I. TOXIC0L.-TOXIN REVIEWS, 17(3), 405426 (1998)

.\BSrn%CT

Spider venoms and toxins arc: useful tools for the study ofion c h e l s and s\naphc hctions ofneurons

vertebrates and invertebrates. 'Ilie components ot spider venom. such as protks. peptides. phimines and

bioamincj arc: specits-spdic. The various functions olthest: touns are raiewui in tlus p a w .

INIROI)I x-rioiv

.4hout u).OOO s p i e s ofspidm have k e n dwti lxd throughout the \\odd (1). most ofnhich are hmnlcxs to

humans. CX those. onh. 180 species bite man and o+ a fw arc:

truly venomous. examples of which are the \\idon slndcr

spide@). 1.200 species of spiden have hxn reported in Japan none of which are venomous. Honever. in the

autumn and Winter of 1995. some wide\\ spi.pitl~!. the red h a d spider. Lcrtralcctxc ha.whr. .md die hr(mn

widow spider, LxrtmJcecfio geonietrmo. wax found in Japan (3.4).

venomous. Honever. m e s p i h are

5 h e l - w h spider. h m n a spider and recluse

There haw ken many r a i z w s on venomous spidm and, or their to-shs (5- 15). espxiau\- on the neurotosin of

black widow s p i b which W: a high molecular tw&t protein m e d dpha-htroro.xin (16.17). Ihe chemical

properties of the toxin of the red back spider \bliich !\a$ introduced in Japan m a studiwl and found to k almost

the same as those of the Ausb;lhan ~d h a d spider to.* which was u -latrotoxin (18). Rumtt\.. however. the

Copyrighr 6' 1998 hy Marcel Drkkrr. In'

405

www.drkkrr.com

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406 OR1 AND IKEDA

study of M e s s spider toxin has become active fmn a neumbidogical -1. Spider venoms are a rich

source of potenbal prohes for ion channel and recqtor m neuron= (1 1-11.19).

l.Spider bite and classi6cation of spider toxin

Intosiwtion pToduced by a spider bite is called arachnidism, arannSm or aaneidism. 1i.e a x of the opinion that

it would k m m appropiate to usz the t m s aranekm or arancidkm introduced m 1910 by S m e r and

Cntcco. rather than xachnidism since the order .4rachnida includes not only s p i h but scoqkr~s.

pseudcsco~piom ticks and mites. Ihc androme c;1uwl by a pt~cular s p i e s of spider is known by term$ such as:

latrodzctism. chincanlhtrm loxosczlism ctmiqm. etc.. particular to that sp ies . Among these. latrodwtisrn

c a u d bq the bite of the black widow spider. is the most fitqumth found form of.araneiq not only in Eumpe

but dso in the VS.k latrodectim ha. been ewmiveh studied since the dassical study of B a a (20). vho

aUofied a black widow spider to bite hi3 finger.

LAe other wmom~ spider w ~ o m s m quite complex and contain a varizty of protein and nonprotein

componennts. .Ihesz componmts include aterase. hyaluronidase. phosphdiateraw. pmtase. G.lEi.i

lustaminc. smotonint.. sp2rmine. pohamina. nuclzotides neuroto.xin3. inwticidal to.siw. and nzcrotiong tosins

(9). The wjor hiolopi.al actkih wicks in the prottvl componmts. In Table 1 we haw classified spida to.-

accordmg to their major componmt and the action ofthe toxin.

Biochmicd pn?pda and thc molcwlar shuctun: of spider vmoms w w little known until 1 WA. hause of

the s d siiz ofthe gland producing the wnom fmn which an insufficient amount of venom could k exiractcd

for ,uwll\si. .At that time. t ~ h n i q w for a d y k w a t p r and not adequate for e.i;anining such small samples.

2.NeurotoNn

2.1. Black \+'idow Spider Ycnom

Widow s p i k which klong to the genus t,drafechLF, are combfooted spidem ( F M Theridiidae). 'There

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SPIDER VENOMS AND SPIDER TOXINS 407

are 40 species of this genus worldwidz ( 1 5). .Among th~x. the . b e r i m blach widow spider. /.u/rahchu

tnvcckziu. hleditmanm blach widow spidn: and /.dtr&chfi tredecnngIiftdhis are we1 hnown.

In 1976. studies of Mach widow .spider vmom and widow spider Inologv \yefl: extmsiwely raiewed by hlaretic

and Ixhez (6). However. sin= that b e thtrr: h.w~ hwn many important studies of hfeditmanean black widow

spider venom.

\'momow effects: In an early study of LtmdectiSm by the American blach widow spider. Ldmfech45

nr'zctmr. Bogen nported 150 caw with 12 deaths tiom the LIS.4 and Canada, the majority of these cases were

males fian Cdifomia who had brxn hitten on the p m i s or adjacent @ while sitting on the seatr of outdoor

prkies (21 ). &hen and Gomez ( 10) notd that wt.ll-conbpUed experiments with widow spider venom were first

done by D',bour ct al. (22). Venom glands h m .berican black widow s p i d m were macerated m physiological

salinz and injected mtraperitondy mto young adult rats. The venom was found to be 15 times m m potent m

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408 ORl AND IKEDA

terms of dry wRght than the venom of the prairie rattlesnake. The firsi signs of mtoxicaiion were stif€i~es of gais

awiwardness of mowmalt pm&mmantly in the hind limbs, lacrimatiq and closure of the eyes. The m& would

mnain immobile unless disturbed I.spiration was labored or shallow. and all died m 8-36 hr. Sampayo, m a

thorough account of the pharmacological actions of the venom. umcluded that the venom’s princtpal action was

on the cenbal n m u s system (23). Cantm obsetved that the venom abolished conhraction m response to mdimt

stimulation m the p h c nennedqhngm p a t i o n of the rat. He concluded thal the m o m had an irraersible

blockmg effect on the motor end plates (24).

In 1970, the effect of the to.dn of Ldwxfectzu was demmiraIed on neumnuscukr ImkUn&on, a sm$e

neuromwukr*ction of thc sutorius muscle of the ffog. The resuh showed that LutrdchLs venom m fhe to

t e n ~ ~ e s m ~ a n m c ~ e a s e o f t h e m i n i a t l r r e e n d - p l a ~ p o t e n t i a l s ~ P P ) ~ 0 . 5 - 1 . 5 / s t o 3 ~ 1 0 0 0 i s . After

reaching the p& the MEPP frequency fen to a low value. less than lis. The amplitude of end+ potential

(EPP) h t incrwsed by samal mcmnents and then fen to m. The nem ending spikes dwppwd at

appmximately the same time, probably due to depohization of the n m endmg The authors atbiiute these

fin+ to the venom wtmg with the nem en- membrane and the release of transn&a substance. This

release of hanrmiter occlared mdependenUy of the presence of calcium ions and mdepencidy of the

depdmuation of the endmg (25.26).

& mom caused n e m m n m depletion on not only cholinqjc n m terminals but also on adraKlgrc

(28). The exfract depolarized the c.9 nem fibers m the rat nis (27) and tnminals ofseveral mammahan .

body of the Crayssh stretch mxptor (29) and induced a disc- of impulses m the axon (30).

Venomous component: The venom i multicomponenS with some of the a c h a g e n ~ found to lme

characrerish of ptein (31.20.22). h4any workers anRnpted to analyze the protern toxin by elecbuphmm in

196O’s, but these methods were not as good as at present and the imp mi^ ofexiracts of the venom glands tamed

--. Among these studiq sigli6mdif€erences in p t e i n composmonofglandexhacolm

dammk&d among four SpeCKs o f h d c t m : L.mactans, L.variolus. L.gemet r im andL.bishqi (32).

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SPIDER VENOMS AND SPIDER 'IDXINS 409

Table 2. Toxic elTed of various fraaions of the LuhnhU venom (34-35)

Fraction Fm Mouse Howflv CW6SIl 1964i331 197x34)

hole + + + +

extract

A A

B + +

c + + i LVI C

LV2 B

D

E ND +

B5 + + LV3 D

c 3 i ND

c5 + + ND

E2 ND + LV4-

Fractions .A-E O f Li lPdc t l c~ venom^ were referenced h WO& in 1976 (35).+, active; -, inaCk, ND,

not determined. LVl-LV4 were hctionated m 1964 (33). A-D were fiaclionated m 1972 (34).

Since the mid-196O's gel filtration and ion exchange chromatography m e t h d haw been &Iy used for the

separation and puiiication of proteins. "hole eidncts of m o m glands haw been fractionaid by these

techniques. Thae are: (1) h t i o n hamg no toxicity m houseflies and mice, (2 fraction with hgh toxicity m the

ling mouse and guinea pig but nontoxic for houseflies, (3) fixtion pmducing quick paralps m houseflies, (4)

h t ion hamg a slow toxic action on howflia and (5) fiaction hacmg toxicity on the rayf fish &etch receptor

(33-35).

F'unfied protein fixtion B5 which waq active against vertebrates was named atpha-lalrotoxin FractionB5 was

responsible for both the inc- m the firquency of MEPPs and for the depletion of Vesicles (35,16).

Study of LTS (a-latrotoxin): LTS mterac& with hpld bilayers to make them permeable to certain ions and

appears m selective for alkali catim over anions. The bilayen &hiteIy become permeable to Ca(IQ

suggesting tfiat pennanent channek are f m e d in the &id bkqa by LTS, and that these remain open (36). It w a

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410 OR1 AND IKEDA

also found that LTX pmmted the uptake of labeled garmna aminobutyrate (GABA) and norepinephrine by rat

brain synaptosomes. The relea% of GABA that stimulated the LTX was MI dependent On extTaC&h ca@).

The release of norepinephrine was Ca(Q dependent (37). The LTX stimulated the lease of transmitt-

dopanrine and norepinephrine in a neurasecrekny cell h e (PC12) derived h rat phenochrmnocytoma in

culture (38).

The amino acid canposition of LTS, labeled LV3, was detamind with a Becl\man model 120 amino acid

analyzer and found to Consist of 1219 residua; SDS polyac~lamide gel elec!rophd meald its the molecular

weight to be 130 kDa (39). Variable results of the amino acid sequence of the LTS have hrxn reported by Russian

worlcers (40). Thereafter, the total amino acid sequence of the LTS was deduced h cDN.4 sequencing

(41).The cDN.4 conIajned a 4203 base-pair open Eading kame wmsponding to the 156 855 Da pottin

“mposed of 1401 amino acids. Molecular w@t differed 6om that d e r determined h means of SDS gel

electrophoresis. Thafore. the toxin can be umsidered as a precursor. and processing taks place m the C-terminal

region of the pb+phde chain duing its maturation. This hyohesis seems more remnable hzcaw all studied

peptides of hyptic hyddyate are equatly distributed m the toxin kagnent with coordmats 1-1 170. h folecular

mass of this fragment (Mr 131 ma) is in good ageanent with the apparent molecular mass of the isolated tosin.

Moreover, t h e C - ~ ~ e n t o f ~ ~ ~ ~ a m i n o a c i d ~ d ~ ~ i t h ~ ~ t ~ 1171-1381 wasabsentmthe

products of toxin tryptic hydrolyate despite many cleavable regjons (41). The

were found to Contain two components: polpeptidm of 1401 (alpha latrotoxin) and 70 (low molecular we@

protein) amino acid r e s i k (42).

purified toxin preparations

The LTX is thought to act by bmdmg to high-afiinhy receptors which are found in susceptible tkwe~ (43.44).

This -tor is a member of the nem.xin family of proteim (45) and i found m the membranes of pres?mptic

n m tRminals where it interacts wim synaptotagmin (a synaptic vesicle protein) (46). This nemxin-

~~ complex is thought to be inqmtant m neurobmmitter secretion (47%48). It has also been suggested

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SPIDER VENOMS AND SPIDER TOXINS

that neurexins are invokd in cell recognition in the ntmous srstffn (49). The low molecular we& protein named

labdectin Contains 88 amino acid residua. hut a fragment of 18 amino acid residues of the protein is lost after

protein maturation (5b52). Thk protein ehbits catain structural homology with erabutoxin-a ffom the sea snake

(42) and with the crustacean hypqJycemic hormones (53). Struchml analogy of two p r o h is not n&

3ssociated Rith functional similarity. The function of latrodectin is not clear.

41 1

Anempts b e hxn made to identi@ the other hlack widow spider venom fractions n i c h are responsible for

the effects observed on btxtebrate tissuerr. .A protein with a smgle hand alpha-latroinsectotoxin. waq identilied as

h i n g a molecular w w t of 120 m a . Latminsectotosin has an amino acid content similar to

acts as a spzcific &toto.& causing rapid trammitier release 6om k t nerve endmg (54.55).

of LTS and

2.2. Studies of Sydney funnel-web spider venom

‘The Sydney h e l - w e b spider. .4@m rhiw.hrr. may be umsidered to be the world’s most dangerous spider

kause of its Fbength and appxsiveness. the lethal potency of its venom its nocturnal habits. and its penchant for

invadmg houw. It9 dwbibution coincida rvith the metropolitan area of Austraha’s largcjt city.

\.enornous effict: The venom produces 3 qndrome charactaid hy gen& m w l e fasciculation

sweating, &ation hyatmsion and tachycardia (56). The venom We the hlack ido ow spider venom i n b a

masskt release of neurohmsmitier 6om motor end phtts and nave temdnals throughout the autonomic n m u s

ysttm. L[n!jhe Ridow spider venom its e f f h are transient and mwsihle. They can he blffihed m Vitro hy

gallamme. sumethoniwn lgnocaine and diaztpam ( 57). In contrast to the widow spider m o m its m o m has

little effect on the ultrashucture of n m e e n h m irolared rat diaphragms and that is no ohvious depletion of

synaptic vesicles f?om the trmdnals (58).

\.enomow components: The lethal neurotoxin fiom the venom of the male Sydnq fimnel-web spider,

rohustoxin. is a pohptptide of 1 2 midues which was isolated and its amino acid sequence determined (59). Che

of related species is Hcafro~che (recen@ transterral from the gtmw~ltrm) vmtus. which is lowled III the

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412 OM AND KEDA

-west of sydnq. mkhdneurotoxinfrmnthemm~ ofboth themale and fd, wm06R is a

pohipephde of 42 r a i h . Eght of the 42 residues were found to differ between mbwloxin and ~ ~ 3 ~ I ~ x i t l . The

two toxins were bghiiy folded polqpephdes (60).

s d other mnponents m propetties of maie ~ t r m * robushts m o m have been reported These inch&

GABA, pennine Complex, Lack acid TrimClhykdyI or pentalhmpp '.matedenvativ% cibicacid. &cm4

urea gtucose, gtycme, spermidine, thyantinz. and octopaminz.

2.3 Ctenid Spider Venom

In B M most cases of env.motnation by the spider are caused by Phoneirtrro nigrnwnter (F@ Ctenidae).

\.momow effects: Neurogtmc shock a n be observed mox kequently m children and is characterized by cold

agibtim &atim Priapism and death. 'The effect of m o m on the twhed auricle of guinea pigs k

produced through the release of acevlcholine and n- neurotxmmitters by the ppmpathe t i c and

sympathetic m c t d . This release owm by the action of the venom within the sodium channels of the

1\2~e tenninal mtmhran t : (61). Tlws effsts are abolished by tetmdotoxin (62). tiowever, there are mriom

polypeptides m the m o m which have pattcular functions.

Vmomous component: The wnom of Plmmitrro nrgmenter contains histarnine. Serotonme and other

polypeptides (63.61). The contnction of.the rat chaphragm mduwd by the spider bite was due to the release of

acetylchohe by a basic component that would be separated by paper electrophoresis (65). Three neurotoxic

fractions (PhTxI.F'hT~PhTx3), lethal to mice, were iwlated limn the mom by gel filhation and reverse phase

chromatography and the complete amino acid sequences of 1 1 pepti& were detetmined to be limn 32 to 77

amino acid residus (6266-68). PhTx.3 blocks the nemuscular hansmission of skeletal muscles by acting

prejunctiody to deprrss n e r v e d e d transmitter mlease. The effect was r e W to a d i m i n d d

the nene teminal a4sociated with inhihiton exocytosk (69).

entry into

The venom of the neohopical wan- ctenid spider, Cuprennw saler. contained pmteim and peptides some

with enqmatk acaity. ofhem with a neuTotosic mode of action, and s e w d as neurotoxic ac(inp low molecule

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SPIDER VENOMS AND SPIDER TOXINS -

413

masssubstances. 13 pepiides(CSTX-1 toCSTX-13)hadtoxic i tyofvarious~ withthemttoxicpepbde

bRng CSTX-1 and the least toxic peptide, CSTS-13. CSTX-1 has a sequence of 74 amino acids. CamparisonS

of the amino acid sequences of thk toxin with those of the closely related ctenid spider, Phoneutna nrgnwnter,

showed no distinct sirrtilaritv m nine of 17 -revealed some N-texmi~I srmilanty with six out of 17 amino

acids, and complete identity m only two cases (70)

2.4. Chimcanthium Spider Venom

Most cases of mumat ion by spiders m Japan are caused by Chirocont~iJum,~aponJ~ini.

Venomow efficb and components: ?Ids w o m was purified with ion exchange gel chromatography and the

toxin was determined to be neurotoxic m action. 'The toxic responses m mice were dyspntx pr0Sh;ltion tlaccid

paraiyw and death. The minimal lethal dose of the purified venom for mice was IOf.4. The relationslnp between

lethal Qse (LD) and time to death showed conelation m dosa firm l0f.i to 155fA. The LD50 against a house

fly was 0.069fA. The molecular waght of the to.& wiu dettermined as 63.(Xx)+ 2.(W by SDS polyqlamide gel

e l e c t m p h d (71). The toxin has not been analyzed vet.

other components of the mom haw been qmtd noqinephrine. epinephrine. octopamine. serotonin

spermine and histamine (72). These catecholamines and hislanine c a d mure pain through the spider hite.

2.5. Orb H'eaa\ing Spider Venom

Polyamine Toxin and Glutamate Receptor

Jn 1982, a neurotoxin h the "Jon spider." .\'eph/d c/maa. was newly found m Japan. The t0.G named

Jon spider toxin (JSTS) is an une,spectdy loa molecular weight substance (ca. 600 Da) which acts

posbpapticaUy to bloch the &tamate receptors in the crustacean ncurmuscular qnape (73). Similar

postsyqtically-acling toxins to JSTS have suhsequentlq. been found in many other &web spiidets and their

sbuctures were contimed by chemical +sis and mlR. These include the to.xim of the venom h ArLmeus

ventncmus and Nenscuna nmhco (74). NSTS (h .Vephrh nldmdata) (75X and WopiIl (firm,Jrgiope

l&m) (76). These polyamine-toxins consist of an ammatic subunit amino acid linker, and a p o l y h e side

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414 OW AND IKEDA

a-Aga-IA

Sbuchm

Effect padyk effect on insects

Action

heterodhebic peptide cmsihng of 66 h o aoids

blockade of Presqnaptic ca@) chermcls m insect

m o b m e m e ; fhUy blocks hgh threshold currents

a n d m ccc- T-type c m t s m rat sensoryneurmes

o-&a-IIA

Smtm notdebmined

Effect para?vslsinmsects

Action blocke Ca@) flux m both chick (homogenous N-channel)

and nt (almost P-channel) synaptosomes

0-Aga-IIIA

StlWtUt

.4ctim

pepti& of 76 amino acids

non-selective Ca(lI) channel blocker, Vohassdependent

blockade of L-,N-, and Pchannels in rat n e m e

0-Age-IVA

Structure mde of 48 amino acids

Action ~ele~tkb blocks P-type C a O channels

blockade of &tamate r e l w

depolanzatlon unblock phenomenon

blocb presqnap tic Ca(Ir) channels at manrmalian n e m w u l a r p c t i o n

0-Aga-IVB

SbuctUt

Action

peptide of 48 amino acids (closely related m size to mega-Aga-WA )

hq& potent blocker of P-type calcium channels m rat newma

chw. Sonte of these to& were q n t h d (77). The JSTS adogue, 1-naphtyl aceiyl speMine (Naspn), was

s y n t h e s i z e d and

glands of Nephh chars were idenl3ied and s q n t h e s i z e d (79). LJV-spectra enabled the cIa&icalion of the

mom components into three types: aopin, argiolrmihs, and pseudoa&phh. M~Iecuhr massa of h e

for finther study ofgtutamate -tom (12,78). Additional neurotoxins h m m

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SPIDER VENOMS AND SPIDER TOXINS

compounds a~ Withm the 630-759 range. and only ~udoargiopinin III has the s d e r mas9 of 373. ..\mino acid

analysk revealed atgirdne and asparhc acid residues in the majoriw of the w o m components. ;U arghhes

415

posszss a free amino g-oup(80).

The m m immotnhing effect of the venom 01 the othcr orhweming spider. Argiqie hntennichr. on the

Wkr03Ch and the common meal k t l e Ls far more devant to pm capture than to causing death. 7hLs ne;&

effect on k b s adzquate. considznng that tlic method of hunting includa \napping up the prey hefore hiting

(81 ).

2.6. knerican funnel weh spitler venom and the neurotoxic peptide

The .hmniwn h e l - w e h spicla. .4g&myi,\i> q w m , ~mwsscx a mnaAable .may of biological achities

when msidaing both v~atetnatc .and inwichratc s y t ~ m s .

The spidt7 has SLTLA to.^. dagnated ;giito.xins. \\hich are of inter~xt to neuroscientists stuthing dutamate

receptois and c'dn) cham& (82.83). -Ihc pcptltlc /C"N omqg)- .*-n-.i has hcen identitie:tt as a potent

selectiw blocher of p - 5 ~ dc ium channek (84.85). lhe poh.amine toxin I ; 7 S i also found in tlie vcnom. FTS

is bztiwed to szlectiveh hloch €'-channel\.

From the Japanese funnel-web spda. . I ~ e l r . n ~ r Opi//&'17fd. \w tsolated the to& a&min which

had 38 residues and blocked the @m$miner pres:mpticalh at the lobstcr neuroinusdilr.iunction( 14.87).

Plectoxin from the venom of tlie primitiw hunting spider. f/ecwex\ rmn! (I.'.* Plectrcuntbe). \\as

bioa%Fed and purified to 9 pzptides. Ihu anuno acid wqumces of 7 ofthe 9 pcptides RQY de tmned . hlosl

peptides WLW short (46-49 amino acidq) and shoned vari'hk s p i e s spwficih (XX).

The venom of the cellar spidsr. Segrsfrm f h ~ v 7 1 1 n ~ z . cauwtl the dqwbriz3tion of ewtahls mmhrLanes. on

increase in the szcrction of mediator. and a prolongation ofthe action porential through the inactivation ofthe Sn

channels. 'The complete amino acid squ~mc~x of the insdotosin of the venom i 35 residues (89).

Ihe venm of the funnel weh spider. / ~ ~ I ( J / L w ~ I ~ 7 1 m 1 1 . contains a mk-turz of compounds. ( he inse:ctici(kd

peptide that contins 38 amino acid5 and 10 acylpohaminr toxin$ namd curatoUns WLX purified. lhe

acyipdyamines instan@ pai-abzed Iepidoptn;an Iam;ic following injection (90).

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416 ON AND IKEDA

2.7. Tarantula Spider Venom

The tarrmtula is a hge spider which belw the Fam@ Theraphosidae and has as b habitat a hole under the

ground Tarantula spider venoms contain variouS componentr such are bioarnina polpnhe8, adenosine

nuclmtides and proteins (91,92).

The venom h the Mexican red knee tar;mtula Brociypeln~o sm/iirr. is considered not be hazanlous to man

Two pmth of the toxin werz isolated and sequenced F’mt&-l has 39 r a i k inchtdmg Six cyteine raidues

with three disullide bonds (93). It is identical to one of the iwfinms of cockroach-toxic ESTS kom the m o m of

an& tarrmtula E t r ~ p l m a cc7/~f0rnricn1. h t contains 39 d w (94). protein-5 has 34 r a i k including six

cy& residues vith tluee &uifide bonk and is most simila~ to TsZ-9 fmm the Brazilian ‘armed‘ .spider.

a l t h 0 u g h i t h a s ~ 4 1 ~ o ~ ~ c e i ~ t i ~ ( 6 6 - 6 8 . 9 4 ) .

The venom fimn the C%ex b id spider. S e h n m w m /novena. which hes in hoks mdegmmd m the swth

of C%na, cilllsed paratyas ;md rapid mspb?tny failure m mice (95). Neurotoxic component^ were proteim.

.bong the neurotoSic COmponenIq wa hiwentoxin-I. a peptide of 33 midue% isolated f b m the wmom. The

sauctun: ofhuwento.uin-I was similar to p-agatoxin \’ fjmn the h e 1 web spider. .i,qeIenopm uper/d. which had

thra: d i d & honds. HOWWLT. the hi~logical acti\.ititS of the two to?Cms %.t= @Z & m i . HiwentOxin-1 W ~ S

show to m i b l y block the neummwular transmisiion m an Ldated mouse phrenic

Preparation (%) and the p-agatoxins are knonn to he insecticidal nemto.sim. wtuch can mduce firing

and ma& hmmitkr release fmm p y a p t i c s t o m at the neuromuscularjunctitm of insects (86.97). A sw

of the three- SIIW~UR nf hiwentoxin-1 is m pmgttsq (98).

3.Necrotoxi.n

3.1. Recluse Spider Venom

Rahrse qndm (genus h a w l e ~ ) are cosmopolitan. found in urban mvhnnents and make mtgular web

structures That are m excess of 50 species only a few of which have btxn impbred m loxosceb.

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REFERENCES

1. Platnick K.1.. kkanws in Spidm ~1;~~onomy. IOXX-1991 . The New 1 . d Entomological Society. lu'w

Yolk 1993.

Yoshilura hl.. Spider Hioloq. C i a h i S?uppan ('enter. 'I'oh?o. 19x9.

Cho. 13.. R w d s of La/r&cm.s ge.eoiiretri~7o (.heae:Th&&dae) 6om Japan. i\cta Arachnol.. 34:167.

1995.

2.

3.

-1. (hi hl.S& E. md &eck ti.. Introduction of widow spidm mto Japan. Mcd. Entomol. 7ml.. 47:111.

1 %.(In Japmlzsr)

Tox

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418 OR1 AND IKEDA

5 .

6.

7.

8.

9.

10

I 1

12

13

14

Tw AT.. \'moms: Chaniihy and hlolecular Biology John Wdey & S o n s hT, USA. 1977.

Rlaretic. L.. and Lzkz D. .&antism. \Vith Special Refmce to Europe. Natl. Librat?/ Med.. Behesda-

NOL.IT. B q p d 1979.

hlmtic..Z,. Spider venoms and their effect IY Ecophysioloa/ of Spidtm, edited hv W.Nenhvig p.142,

S*m-\'2llay B& 1987.

(hi RL.. Biologv of and poLoning hy s p i h . In Handbook of Natural Toxh%Vol.Z.edited by A.T.Tu,

p.441. h h d DeMm Inc. LT. L'S.4. 1984.

C m ('.R.. and ()dell. (3.1. .. The biochemishy of spidervenms. In H a n d h k of Natural

Toxim.\'ol.Z.t.dited hy ~XT.Tu p.441. hlarcel DeMer, h e . N1: LISA 1984.

DuchLn. Id.\&. .. and Cmez S . . Pharmacologv of spider venoms. IN Handbook of Natural To* VoI.2

edited by .A.T.Tu p.483. hfmxl kUer Inc.. New Yo& 1984.

b w a i N.. Brain and 'Tosin.. ,.lsaliura ShotenTohyo. 1990. (In Japanese).

Lanai. N.. hliwa. ,A. Shimazahi L., Saham,Y., Ro- HP. and N a h h T., Spider to& and

glutamate receptors Comp.Biochem.Physio1.. 98:87, 1991.

b w a i N. and N a l a j k T.. Neuroto?;ins kom spider venoms. IN Natural and Synhetic Toxins, edited by

.-\.L.Fkq.p.319. . A u M c hs% Inc.. London 1993.

Kawai N.. Brain:Rloleccular Biological View, Lodan-sb Tohyo, 1994.W Japanese).

15. \%bite. J.. Cardoso, J.L.. and Fan H.U'.. Clinical toxiwlog~ of Spider bites. Ih- Handbook of clinical

'I'osiwlologv of Animal Venoms and Pois0ns. edited by J.Wtite, p.259, CRC Ress. U S 4 1995.

16. Tzmg M.C., and Siekaitz P. The effect of punlied major p t e i n factor (alpha-latrotoxin) of black widow

spider xnom on h e releast: of acetylcholine and nonepinephe 6om mouse cerebral coltex alices, Brain

Ra.. 139:190, 1978.

17. RosenWL.. and hleldolesi. J.. .441ha-larrotoxin and related to.* Pharmac.Ther.. 42:115. 1989.

Tox

in R

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ded

from

info

rmah

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care

.com

by

UM

EA

Uni

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/18/

14Fo

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al u

se o

nly.

SPIDER VENOMS AND SPIDER TOXINS

18. HiraolaT.. hobaya$h M.. Sadahiro. S., and A g u N., Protein components and toxiciv ofvenom gland-

419

emact in the red hlach widow spidm. Lc l / rdech~~ i?ase/h~ collected in osal\aCity. Japan, Med Entomol.

2001.. 47273. 1996.

19. Saccomano. N.. and .4hhianian h., C'a(I1) channel to?dns:Tool~ to study channel shuctllre and function.

Drug Melop. Ra.. 33:319. 1994.

20. B a q \ \ . J . . Effect of bite of L&c&cho ~ m c / m \ (Fahricius). J.Paas.. 9:161, 1923.

21. Bogn. E.. .kachnidkrn.Spiderpoisoning .~~l~.Int.hled..38:623, 1926.

22. D'.\mour. F.E.. Bzchzr. F. E.. and \.an Ripx I!'.. The blach widow spider. Q. Ra.. Biol., 11 : I S . 1936.

23. Scampayo. K.R.L.. Phmcological action of the venom of Larul'echLr VUC~CJPZS and other Lah.odectus

spidm;. J.Pha~m.Esp.Ther.. 80:309. 1 944.

74. Cantore. G.P.. Conhibuto d o studio dell-ahone farmacologica &I velmo di LL7tr~fecho. rreJenmuguftutu

Kc~si. b. Parilrsitd..l9:158. 1958.

25. I.ongmechzr. Jr.. H I . . Hurlhurt. W.P.. hlauro. .A. and Clad,. .\.N'., Effects of black widow spider venom

on the fiog neuromu$cdujunchon b.ffbts on end plate potmnti;ll miniature end plate potmtial and nerve

terminal sphe. N a t m . 225:701. 1970

26. C'larlc ,A.L\'.. hlauro, A. LongmecherJr.. H.1.. and Hurlhurt 1V.P.. Effects of black widow spider venom

on the 6% neuromusularjunctio. Efiects on the line sbuctun: of the 6% n e m u % ~ j u n c t i o n Nature,

725:703. 1970.

77. Frontah. N.. ('ateclioLamine dzpletmg uffccl of.bkich widow spider worn on iriq nerve f i b . Brain Res.,

37,146. 1972.

28. Frontah. S,. (kanaI~ F.. '1- ilk,.. 'and 13e11ino. 31.. C'atecholanune depleting effect ofblack widow

spider vmom on 6hm innmabng & m t guinea-pig tissues. Espnimtia, 291 525. 1973.

'79. b;awai. N.. hlauro. ,A. and Gnmdef& €1.. F.ffec& of hlach widow spider venom on the lobuster

neurornus&junctions. J.Gzn.Physiol..M):650. 1972.

Tox

in R

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ws

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ded

from

info

rmah

ealth

care

.com

by

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Uni

vers

ity L

ibra

ry o

n 08

/18/

14Fo

r pe

rson

al u

se o

nly.

420 OR1 AND IKEDA

30. Gmsso, A, and Paggi P., Effect of L t r d e c u rnuctam tredecrtngultahu venom on the crajlkh shetch

receptorneurone. Toxicon 5:l. 1967.

31. KeUaV.L. , SpiderpoiSon J.PanSitol.. 1:107, 1915.

32. h4cCrone. J.D., and Netdoff. hl.L.. h immunological and electrophcnetid wmparkm of the venoms of

the North h n i c a n Ldmdech~s Spidns. TosicOn 3:107. 1965.

33. Fmtali N.. and k s . , .A. Separation of thra: tosicologidl) W i t protein C O ~ ~ X I ~ S from the

wnom of the spider I,~itra~ech~.s tre~~ecinr~mtt~?h~.s. . h h . Biochm. Bioph>s.. lM:213, IW.

34. Granata F.. Paggi P..Fmtali N. Effects of chromatographic fractions of blach widow spider m o m on m

bih-0 hiological svstems, Toxim. 10:551.1972.

35. €+ontali N.. C’euxd l i . B..(;orio. .A. Rlauro. A..Siehaitz I’.. Tmy, hlu-C‘h and l-Iudbut\V.P..

purification from black widow spider vmom of a protein Pictor causing the depletion of syaptic vaicla at

neuromusc&.unctiow J.C‘ell Bio1..68:362. 1976.

36. Finlielstein .4.. Rubin L.L., and Tzeng h1.C.. Blach widow spider v~mom: Iiffect of-purified to.6 on lipid

bhyer membranes, Science. 193: 1009. 1976.

37. Grasso. h and Semi . M.J.. A toxin purified from the venom of black nidofi spider aEects the uptake and

release of radioactive gamma-aminohutyate and 3epinepInine from rat brain qnaptosomes. Eur. J.

Biochem. 102:337. 1979.

38. Ckwo, A. Alema S.. Rufim, S.. and Senni. A1.l.. RLich widow spider toxin: Effect on catecholamines

release and cation petmeability m a ncurosecretoq? ceU line (PC 12). In Natural ‘Tosins. edited by D.EXes and

T. Wadstrom, p579. Pergamon Press. NewTorh. 1980.

39. Grasso. A. F k p d o n and properha of a neuroto.6 purified from the venom of black fiidofi spider

(LaIrafeeha m m t m tredecimgul[Lctus). Riochm. .Biophy. Act& 439:106. 1976.

40. Salikhov, S.. Taslrmukhsnedov. hl.. Adylbehov. M. Athdhanov& .I.. I;omzq.w. .4.. and Sadykov. A.

lfolaton and structural study of neurotoxin fimn the venom of spider htrakchLY tredec1nrgumh~s. (‘hem.

Tox

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from

info

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ealth

care

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by

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Uni

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/18/

14Fo

r pe

rson

al u

se o

nly.

SPIDER VENOMS AND SPIDER TOXINS

Peptide F'mIeins.1:109, 1982.

41. IGyatlrin N.L. DuIubob;l, LA.. ChekhoAaya 1. A. and Chishin E.V.. Cloning and sbucture of cDNA

XI- n -lah-ot~Sin ~IVIII black Widow spida ~ e n ~ n FEBS Lett.. 2701127. 1990.

42. IGyatIiin. N.L. Dulubow. LA.. Chel\homIqa I. A,. lipkin A\'., and Grishin E.V., Shucture of the

moledu wclght protein copUritied Gth/i,-latroio,* Tosicon 30:771. 1992.

42 1

-13. Sheer. H.. and hleldoksi J.. purification 01 tht: putatbe R -Irrtroto.sin meptor 6om b o h e s~maptOs0m;ll

membranes m an actbe bindmg ftnm Mfl3( ) J.. 1323, 1985.

U. I W ~ I W .. 4.G.. KovaIdo. 1:. .I.. Shamotido, ( 1.G.. SuIlroba LN..

('hishin E.\'.. Isohtion and pmpda of the ( I -1abr~o.sin mqtor. EhLIBO J.. 92023. I y 9 0 .

T. A.. Lk+ov.Y. A.. and

-15. G q p t Rl.. L k ~ o v . Y . A . , €htaY.. 1)avlt:tov. 13.. Petrenco. A.G.. and Sudhof. T.C.. Nemxim. Cold

Spring Hh.Synp.<huni.Riol.. 5748.3. 1992.

16. I IataY.. Dnletov. B.. Petrenlio. A,(;.. J'lhn K.. and Sudohof. T.C.. Intmetion ofsyapto13gmm with the

cytoplasmic dormlins of new&% Neurme. 10:307. 1993.

17. Pemco. .4.(;.. lazqwa. \-I>. . G~IPCI~. hl , IarqulT. . \loomaw, C.. Lhohhlatchw. .-I.V..

U s ~ o v . Y. A. Slaughter. C.. Na$imov. 1. \ ... m d Sudhot T.C.. Polyeptide composition of the o -

htroto\-in weptor. J. Rid. <'hem.. 20X:lX61. 1993

-18. Petrenw. A.G. Ptxh 11.. Dnleiov. 13.A.. LstiLTov. Y...\.. Geppert hl.. and Sudhof. Bmdmgof

related to then -lamotoxin recep~or ant1 I.miru. Scitme. ?57:50. 1992.

50. Knatkn Id.. Dulubova I . . \ . . and (hliin. I-..\'.. C'loning and s t ~ ~ t u r a l -is ofF,o}-lahw3oIoxin

cI)N.4. . h u n d a n c e o f d ? ~ - & e repeats. tur.J.13iochem.. 213:121. 1993.

Tox

in R

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nloa

ded

from

info

rmah

ealth

care

.com

by

UM

EA

Uni

vers

ity L

ibra

ry o

n 08

/18/

14Fo

r pe

rson

al u

se o

nly.

422 OR1 AND IKEDA

5 1. Pescatori M.. and Grnsso. A,, A huz-specific protein of the venom gland of black widow spider affects CL

-latmtoxin action .h. Nl’ Ad. Sci.. 710:38, 1994.

52. Ptxatori hl.. Hradhur?;. A,. Bouet. F.. Gargano. N.. llaqtrogiawmo. :I., and Grasw. A. The cloning ofa

cDN.4 en- a protein (L~trodectin) which co-puritia with then -latrotoxin h m the hlach \+idow spider

Latrodzc;tus btd&ngullatus(lht7idiidie). Eur.J.Bi~hzm..230:322. 1995.

53. Gaqparini S.. hli\.atljn 3.. k e l . P.. Uoulain J.-C’.. Tacnet. F.. Kipxhe. I’.. Forat. E.. &shin E.. and

lIme7. A. The Ion molecular wiglil protein wluch co-purifies tcith o -1itrotoin is stiuchudj rzhted to

crustacznn h?&canic honnonn. J.Did.C’hm.. 269:19803. 1904.

54. Kovalfishaya G I , . Pashhov. \- 13ulghov. (I,\... Iedora. I.hl.. khgzaruh L.(i.. andCikhin El’..

Ihtification and isolation of protein aIpha-latrohszctoto\in from the \‘mom of spider l~trodectus mactam

hcdccimgukitu~. Riooryn. hhmua. 16:1013. IWH).(in Russian)

55. Slagazanikl..<i.. Fedorova 1.kI.. L;Ovale\slqa G.1.. I’ashhov. \-.S.. Rulgiho\. O.\. .. nndChishin E.l. ..

SelecriV~: pres>naptic ulwctoto\in ( ; i l p l i a - b t r o i ~ ~ t o t o . ~ ) Lsolated from Mad icidov spider \mom

Neurmimce. 46: 18 1. 1992.

56. Suth&d S . L Lsnlation. mods of action and pro~‘0lXrties oftlie m j o r tosin (i\trasolo.~) in the venom of

the Sydney b e l - m e h spidtx (. [fr&n’ rohinhr.$). € 4 ~ . Aust. Soc. Rled. Rw.. 3:177,. 1973.

57. Suth&d S . L . (‘linicd and expaimmtad aspects of arachnid piwning in .4ustdh In

Keurotows:Fundammtal and Clinical :idvanczs. Chuhh. 1.. and <itffm I..B. &. .4delaide Univtmity

Pnx. . lu~trntia p. 1 5 I . 1970.

58. Hadton R.C.. L’ltrastructurz studies otthc action of .4usmlian spider venom. 3D.Ann.Proc.Elecmn

XIicrosc.Sw..h..p.40. 1972.

59. S e m i e l D.D.. Chssms. R.. Uhitelq. N.hl.. and Howden. M.E.H., Complete amino acid sequence of a

new 5~ lethal neuroto.xin h m the venom ofthe funnel-weh spider.i@m rob70h~~. FEBS Letten; 181:154.

1985.

Tox

in R

evie

ws

Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

UM

EA

Uni

vers

ity L

ibra

ry o

n 08

/18/

14Fo

r pe

rson

al u

se o

nly.

SPlDER VENOMS AND SPIDER TOXINS

60. Brown. M.R.. Sheumaclc D.D.. Tyler. h1.I.. and 1 lo\cdzn h I.E.H.. .Amino acid sequence of vmutmin a

423

lethal neuroto.xin fFxn the venom of the tunnel-web spicIzr.ltra 1'eI:whL~. Bioch~m.I..250: 401 1988.

61. LUWS S.. Spidm in B r a d Tovcon 26.75'9. 19x8

62. Rezendel Jr. L.. Cordeiro, h1.N.. Ohin 1.B. . and kniL C.R.. Isolation ofnzurotosic peptides 6om the

venom of the 'armed' spider P/iumwrrr'r rii,grnwter. ToUcon.29: 1225. 1'991

63. Kaiser. I.. C M k P.R.. :%rd S.D.. IIudihury S . Shabanowitz J.. Francis. B.. John T.R.. Hunt D.F.. and

C&L G.1. .. primar? shuctm of two proteins tiom the vmom of.the 1lexic.m red lace tarantula

(Bnre~pe /mr .stnr/hr). J. Toxicol.

61. Duuz C.K.. Separation of proteins and charactaimtion of active substances in the venom of the Brazilian

spiders Anak .Acad.Bras.Cien.. 35:283.1%~3.

65. Banio. A. Spatic action ofthe venom ofthe spid~7fhoneum.r tinr. Acts Physiol.Io!ino Amtxicana. 5:132.

1955.

66. Diniz C.R.. Cordt.ir0. h 1.N.. Junor. I ..R.. Leb. P. Fwher. S. . Reiman. F.. ( )heir& E.B.. and Kichardson

hf.. The purification and amino acid sequences of the lethal neurotoxin Tzl fiom the venom of the Bra2ilian

'armed' spider Plione~ttrw nrgmwi/er (Lqs.) . kT;BS Lett.263:251. 1991.

67. Cordeiro. h1.N.. Diniz C.R.. \.alentim , i .C . von 1;iclrStedt \;.R.I).. C3by.J.. and Ricbdwn hl.. The

purification and 'amino acid squznces of four 1x2 neurotoxins from the m o m of the Brazilian 'armed'

spider Phoneubia nipriV.nt.r (Keys.). FEBS Lett.. 310:153. 1992.

68. Cordeiro. h4.N.. Figutxiedo. S.G.. l'dentim .A('.. Diniz C.R.. von Eicbtedt. V.R.D.. Gilroy. J.. and

Kichardwn hi.. 'Ihe purification and amino acid sequences of.si\; 1-13 b'pz nzuroto.sh 60m the venom of

the Brazilian 'armed' spider F'l~onetctri', nr,yrnwi~er (Kqs.). J. ToUcol. 3 135. 1993.

69. Souccar. ('.. Goncdo. hl.C'.. L,ipn A . J . Ironcone. I..R.P.. 1 . e h 1.. andhlaqoli F.. Blwhde of

acetylcholine re1e.w at the motor endplate hy a pohpytide from the venom of f/ irnwiirrr~r r7rgrnat1fer.

H.J.Pharmai .. 1162817. 1995

Tox

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from

info

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care

.com

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vers

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/18/

14Fo

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se o

nly.

OR1 AND IKEDA 424

70. Nen%L.L, SchaIlerJ., and NmnhvrgK., Purification of toxic pzptidzs and the amino acid seiptmce of

CSTX-1 fmm the rnubmnponmt vmom of C’~gmnma , s ‘ i / e r ( .~~~e:Cten idaz ) . . I’oxkm. 32287. 1991.

bmgenic mines m spider vznom glands of nine typical Japanex species and chromalographic elution paam

analysk ofvenomow components J p n J. Sanit. Zool..42:77. 1991.

73. kwai, N.. &a, A. and A h , T.. Spider venom contain$ specfic receppror blocher of glutaminer&c

synapsa BrainRzs., 247:169. 1982.

74. Kawai, N.. Miwq A, and A h , T., Specific antagonism of the &tamate receptor by an eltract fimn the

venom of the spider Amnew mtrimw .I. Tosicol. 21:438. 1983.

75. Y., Yasuhara T.. Higashijima T.. Yoshioka M.. Miwa A. b w a i K.. and Nakajima T.. Chemical

characmimion of spider to* JSTS and NSTS.. F’roc..Japan .4cad.. 62:359. 1986.

76. Chishiq E.V., V o k ~ T.M., Arscnk. A.S.. Resthetom 0,s.. Choprido. V.\’.. hr ; lgajd

L.G.,hntonw, S.M., and Fedmva I.M.. Sturucture-functional c h a r a c t d o n of arpiopin-an ion channel

blocker fmm the venom of.4rgope loh~ltu; Bioorg. Khim..12:1121. 1986.

77. Ha4hoto,Y., Yasuhara,T.. Endo.l’., Shudo.K.. :imnah.l’.. b w a i N.. and Nalajima. T.. Synthesk of

spidertoxin(JSTS-3)anditFarwlogua. TelrahedmnLztt.. 28:3511. 1987.

78. Chi i T., A k b w a T., hfatsdiawa M., Nkhi h( b w a i N. and Yoshioha hl.. .Total s y t h w ofspidamimne

and JOramine, poiyamine to.xin5 hm the jm spider, hkphrki c/mw/a. Chem.Pharm.Bd..44:972,1996.

79. Tsubokawa H., Ogum, K., Mawawa T.. Nakajima T., and liawai N.. Effect5 of a spider toxin and its

analogue on ghrtamate-activated currents m the

74218, 1995.

CAI neuron &er i s c h k J . N e q h y . ,

80. E.V., VoLkaa and I.M., ..\rsertic; AS.. N m magonkts of glutamate m ~ t m . J .hte in Chem..

8:320, 1989.

Tox

in R

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SPIDER VENOMS AND SPlDER TOXINS

81. Fn&L T.. and Nenh%k\V.. Immohil;ri/ing and lethal effects of spidtr vmms on the wA.roach ,and the

425

common medkde. J. Toxicol. 27305. 1989

82. .-\dam% h1.E.. Bmdohx \'.P.. Hiwgjiil\w. 1 . .and \~tmema \-..I.. tnntqji-~4g?toshs:now4 calcium channel

anhgonkts of two suhfixs &om funnel wA~ spidtr ( .-Ig&nqar.s qiert'i) venom. J.Diol.t'htm.. 265:861.

1990.

83. A h s . X1.E.. Iht7- I.hl.. Rcdy. RLI) . . Ilianahd.\~.. w d R m B.P.. Sbuc~antlpropL7tizsof omtqji-

Agitoxin I\-. a new anatagonist ot I'-&pc calcium channels. hIol.Plwm.. 11:681. 1993.

81. R l i n t ~ lA1.. Lmcma.\~.J.. Snider& f d l . . I ee.T.I>.. RcanB.P.. ,and .Ahs.Xl.l:.. P-fipedcium

channels hlockcd hy the spidcr tosin. Naturc(1r)nd.). 355:827. 1997.

85. Rlintz IAl.. ..\dams. R1.E.. and B e n Ii.l'.. I ' - t \yx calcium channels in rat central and pn iphd neuronm

h'ewme. 9:RS. 1992.

86. Shinner. \V.S.. .\dams. X1.E.. <histad. J.13.. Lahoha. H.. C'en R.I1.. I,ndela F.L. and Schoolq. El..\..

Putification and chctuizat im of two cli~%ws of newtoxins fknn the funnel weh spider. .-Ige/t.nopvc\

'giert'r. J.Uiol.~hnn..267:2150. 19x9.

87. Hagwra. L.. S a h i L. hliwa .I. ,and N,ahajima 1.. Complete amino acid squmw of a new fipc of

neurotoxin tiom the wmm of the spider :I,p/mLi opr/en/d, Binned. Res.. 1 1 :I 81. 19%).

88. ()ui$tad G.B.. and Shinner, A..S.. Lwbtion and squmcing of hwticidal peptides from the pimitive

huntmg spider. P/ec/reic.s tris/rs(Simon). J I h l . C ' h m . . 269: 1 1098. 1991.

89. Saditx. N.L.. \'dims. I ..A. Lornee?. .\.S.. Sad? hov.. and Salihhov. S.I.. Stud? of the toxic: components of

the mom of the cellar spider Sqe.Y/rirr /I~~rm/iii'i . So& J.Bioolg.C'hm., 13529. 1987.

90. -tad G.B.. Reuter. C.C.. Skinner. \V S.. 1)LnrUs. P.A. Su\wnmmpha S.. .and Iu I , . \V.. Paratic and

inwticidal toxins 60m the funnel wch spidtr. / f o / O l e n ~ ~ 7 w / d . J. 'I'oxicol. 29329. l9Yl.

91. C'abhints. S.G.. CehAe. C.W.. Kuo. h.C'., ('han. 1.L HalL J.E.. l ludibwg S.4.. ,mdOdel (3.1. ..

poh-amm;7es in some tarantula vencrmc J. loxicol. 18:681. 1980.

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426 OR1 AND IKEDA

92. Shnner.\{'.S.. 1knnis.P.. I uL.L. ('mcy.R.1 ... and QuistntL( i.13.. ( ' I i m u L n l clviractaization of

06. Liang S.P.. 7,h.W I1.Y . I'an S.. ('hen. L).. and Zhou P., kopaim and m n o acid sequence of

hunentoxb-L a neurotosin purified fiom the venom of the ('hinae l ~ d spider Selenocusniro htnven~z. J.

Tosicol. 31 :%9. lc993.

97. Zhang,D.. ,and Lung,%. ..lssignrneni of.the three dLsul6dc bridges of HuwntotoUn-L a neuroto.xin ffom the

spider Se/ei7o~.mr~ir~r / 17mw'~ J.I'rotcin ('hem.. 12:735. 1993.

9X. Q u Y . . L . i q I'.. Ding, J. . h l a I... /hang K.. and Ciu 1.. Proton nuclear magnetic r w m c e studies on

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