Neurotransmitters

Neurotransmitter Criteria1. IdentitySubstance must be found in neurons

Neurotransmitter Criteria1. Identity2. SynthesisCell has precursors and enzymes necessary for synthesis

Neurotransmitter Criteria1. Identity2. Synthesis3. ReleaseMust be released from terminals; (collect substance from cleft after nerve stimulation)

Neurotransmitter Criteria1. Identity2. Synthesis3. Release4. ReceptorsCross desensitization between substance and suspected n.t.Blockade of n.t. action by receptor antagonistsApplicaton of suspected n.t. mimics action of nerve stimulation

Neurotransmitter Criteria1. Identity2. Synthesis3. Release4. Receptors5. InactivationInactivation mechanism enzymatic degradation reuptake

Neurotransmitter Criteria1. Identity2. Synthesis3. Release4. Receptors5. Inactivation6. PharmacologySame effect on ion channels; p.s.p.s have same reversal potentialsSame effect on membrane resistance and potentialApplied substances must be effective in physiological concentrationsInhibition of degrading enzyme prolongs action of both

Neurotransmitter Criteria1. Identity2. Synthesis3. Release4. Receptors5. Inactivation6. Pharmacology

Acetylcholine SynthesisDegradation+ CoA

Chemicals that Acton ACh Systemsblack widow spider venomstimulates release of AChbotulinum toxinblocks release of AChcurareblocks ACh nicotinic receptorsinsecticidesAChE inhibitorsatropine as antidoteblocks muscarinic receptors

Clinical Aspectsof ACh SystemsAlzheimers diseaseloss of ACh neurons inthe basal nucleus of MeynertAriceptACh agonist

Monoaminessingle amine (NH2) groupCatecholamines (CAs)dopamine (DA)norepinephrine (NE, noradrenaline)epinephrine (EPI, adrenaline)Indoleaminesserotonin (5-hydroxy tryptamine, 5-HT)

Catecholamine synthesis

Serotonin synthesis

Dopamine Systems

Norepinephrine Systems

SystemsSerotonin

Characteristics of Monoaminergic SystemsDiffuse distribution of targetsFine, unmyelinated axonsMetabotropic synapses

Functions of Monaminergic SystemsState phenomenasleep and arousalhungermood

Amino Acid TransmittersExcitatory Amino AcidInhibitory Amino AcidsGlutamic Acid, or GlutamateGamma Aminobutyric Acid (GABA)Glycine

Glutamate Receptor Subtypes

NMDA receptor binding sites

http://www.sumanasinc.com/webcontent/anisamples/neurobiology/receptors.html

Glutamatenon-NMDA receptorsNMDA receptorsNa+ channelsopenCa2+ channelsopen(Mg2+ blockade)depolarizationremovesblockadeCa2+ enterswhen Mg2+is removedCa2+dependentK+ channels openrepolarizationpostsynapticeffects(learning)reinstates blockade

abcNon-NMDA Na+ channels open, Na+enters and depolarizes membraneb. Mg2+ blockade of NMDA Ca2+ channelsremoved by membrane depolarization; Ca2+ entersCa2+ dependent K+ channels open;membrane repolarizedd. Mg2+ blockade reinstatedd

GABA receptor binding sites

PeptideNeurotransmitters(Often serve hormonal functions as well)Substance P (P for Peptide)Principal somatosensory transmitterFirst peptide transmitter discoveredGut hormonese.g. angiotensin neuropeptide Y cholecystokininReleasing factors for hormonese.g. tryrotropin releasing hormone somatotrophin, somatostatin corticotropinOpiatesEnkephalins, Endorphins

Diffusible GasesNitric Oxide (NO)Carbon Monoxide (CO)HemeCO + biliverdinHeme Oxygenase

Functions of Diffusible GasNeurotransmittersregulate blood flowcerebralperipheral (e.g. penis)retrograde messengerHebbs postulate of learning

Summary of Neurotransmitters

Small Molecule Neurotransmitter SubstancesAcetylcholine (ACh)Dopamine (DA)Norepinephrine (NE)Serotonin (5-HT)HistamineEpinephrine

Amino AcidsGamma-aminobutyric acid (GABA)GlycineGlutamateAspartate

Neuroactive Peptides - partial listbradykininbeta-endorphinbombesincalcitonincholecystokininenkephalindynorphininsulingastrinsubstance Pneurotensinglucagonsecretinsomatostatinmotilinvasopressinoxytocinprolactinthyrotropinangiotensin IIsleep peptidesgalaninneuropeptide Ythyrotropin-releasing hormonegonadotropnin-releasing hormonegrowth hormone-releasing hormoneluteinizing hormonevasoactive intestinal peptide

Soluble GasesNitric Oxide (NO)Carbon Monoxide