MECHANISMS OF INTERCELLULAR COMMUNICATION. INTERNET RESOURCES phys/endocrine/index.html

MECHANISMS OF INTERCELLULAR COMMUNICATION

INTERNET RESOURCES

• http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/index.html

• http://www.uri.edu/pharmacy/animation/huangAnim.htm

• http://www.infochembio.ethz.ch/links/en/biochem_hormone.html

• http://www.scientia.org/cadonline/Biology/endocrine/action.ASP

TYPES OF INTERCELLULAR COMMUNICATION

• DIRECT COMMUNICATION• SYNAPTIC COMMUNICATION• AUTOCRINE COMMUNICATION• PARACRINE COMMUNICATION• ENDOCRINE COMMUNICATION

– http://www.wisc-online.com/objects/index_tj.asp?objid=AP13704

DIRECT COMMUNICATION

• GAP JUNCTIONS

• CYTOPLASM TO CYTOPLASM

• IONS

• SMALL MOLECULES IN SOLUTION

• LIPID SOLUBLE MOLECULES

• LIMITED TO ADJACENT CELLS

SYNAPTIC COMMUNICATION

• NEUROTRANSMITTERS

• SYNAPTIC CLEFTS

• LIMITED TO SPECIFIC AREAS

LOCAL CHEMICAL MESSENGERS

• AUTOCRINE

• PARACRINE

ENDOCRINE COMMUNICATION

• TARGET CELLS THROUGHOUT BODY

• HORMONES

• CARRIED IN CIRCULATORY SYSTEM

DIFFERENCES BETWEEN NERVOUS AND ENDOCRINE SYSTEMS

NERVOUS ENDOCRINE• FREQUENCY-

MODULATED SIGNALS

• FASTER ACTING• SHORT DURATION• GENERALLY LESS

DISTRIBUTED

• AMPLITUDE-MODULATED SIGNALS

• LONGER ACTING• LONGER

DURATION• GENERALLY

MORE WIDELY DISTRIBUTED

RELATIONSHIP BETWEEN ENDOCRINE AND NERVOUS

• CANNOT BE SEPARATED ANATOMICALLY OR FUNCTIONALLY

• NEURONS INNERVATE ENDOCRINE GLANDS

• SOME NEURONS SECRETE NEUROHORMONES INTO BLOOD

• SOME HORMONES AFFECT NERVOUS SYSTEM

TYPES OF MESSENGERS

• AMINO ACID DERIVATIVES

• PEPTIDE HORMONES

• LIPID DERIVATIVES

AMINO ACID DERIVATIVES

• SIMILAR TO AMINO ACIDS• BIOGENIC AMINES• CATECHOLAMINES

– EPINEPHRINE– NOREPINEPHRINE– DOPAMINE

• THYROID HORMONE• MELATONIN

PEPTIDE HORMONES

• CHAINS OF AMINO ACIDS

• SHORT PEPTIDE CHAINS

LIPID DERIVATIVES

• STERIOD HORMONES

• EICANOSOIDS

STEROIDS

• LIPIDS SIMILAR TO CHOLESTEROL

• ANDROGENS

• PROGESTINS

• ESTROGENS

• CORTICOSTEROIDS

• CALCITROL

EICOSANOIDS

• LIPID DERIVATIVES OF ARACHIDONIC ACID

• LEUKOTRIENES

• PROSTAGLANDINS

• THROMBOXANES

• PROSTACYCLINES

HORMONE REGULATION

• HORMONE SECRETION INCREASES AND DECREASES

• USUALLY CONTROLLED BY NEGATIVE FEEDBACK

MECHANISMS OF CONTROL

• ACTION OF SUBSTANCES OTHER THAN HORMONES

• NEURAL CONTROL OF ENDOCRINE GLAND

• ACTIVITY OF ONE ENDOCRINE GLAND CONTROLLED BY HORMONES FROM ANOTHER

ACTION OF SUBSTANCES OTHER THAN HORMONES

• CONCENTRATION OF GLUCOSE IN BLOOD AFFECTS INSULIN AND GLUCAGON SECRETION

• CONCENTRATION OF CALCIUM IN BLOOD AFFECTS CALCITONIN AND PARATHYROID HORMONE SECRETION

CONTROL OF INSULIN SECRETION BY BLOOD

GLUCOSE LEVELS • ELEVATED BLOOD LEVELS OF GLUCOSE

STIMULATE INSULIN SECRETION

• INSULIN ACTS ON TARGET TISSUES TO INCREASE UPTAKE AND USE OF GLUCOSE

• DECLINING BLOOD LEVELS OF GLUCOSE LEAD TO A DECREASE IN INSULIN PRODUCTION

CONTROL OF ADRENAL MEDULLARY SECRETIONS BY

NEURAL MECHANISMS • STRESS ACTIVATES SYMPATHETIC

DIVISION OF THE ANS

• SYMPATHETIC NEURONS STIMULATE RELEASE OF EPINEPHRINE AND NOREPINEPHRINE FROM ADRENAL MEDULLA

• WHEN STRESS IS REMOVED EPINEPHRINE AND NOREPINEPHRINE LEVELS DECLINE

HORMONES CAN STIMULATE OR INHIBIT SECRETON OF OTHER

HORMONES

CONTROL OF THYROID STIMULATING HORMONE BY

THYROID RELEASING HORMONE• TRH IS RELEASED BY NEURONS IN HYPOTHALAMUS

• STIMULATES RELEASE OF TSH FROM ANTERIOR PITUITARY

• TSH STIMULATES SECRETION OF THRYOID HORMONE FROM THYROID

• CONTROLLED BY NEGATIVE FEEDBACK

HORMONES MAY BE CONTROLLED BY ONE OR

MORE OF THESE MECHANISMS

POSITIVE FEEDBACK MECHANISMS ARE USED

NEGATIVE FEEDBACK MECHANISMS LIMIT

PROCESSES

MENSTRUAL CYCLE BEFORE OVULATION

• POSITIVE FEED BACK

MENSTRUAL CYCLE AFTER OVULATION

• NEGATIVE FEED BACK MECHANISMS

TRANSPORTATION OF HORMONES

• FREE STATE

• BOUND TO PLASMA PROTEINS

• THYROID BINDING GLOBULIN

• TRANSTHYRETIN

• ALBUMIN

• TRANSCORTIN

HORMONES TRANSPORTED IN BOUND FORM

• EQUILIBRIUM EXISTS BETWEEN FREE AND BOUND FORM

• PREVENTS LARGE INCREASES OR DECREASES IN HORMONE LEVELS

EXAMPLES

• THRYOID HORMONES ARE CARRIED BY THYROID BINDING GLOBULIN AND ALBUMIN

• PROGESTERONE IS CARRIED BY TRANSCORTIN AND ALBUMIN

DISTRIBUTION OF HORMONES• WIDELY DISTRIBUTED

• DIFFUSE INTO INTERSTITIAL FLUIDS

• RATES OF DIFFUSION VARY

METABOLISM AND ELIMINATION OF HORMONES

• LIMITS TO LENGTH OF TIME HORMONES ARE ACTIVE

• ALLOWS MORE PRECISE REGULATION

HALF LIFE

• TIME IT TAKES FOR HALF A DOSE OF A SUBSTANCE TO BE ELIMINATED FROM CIRCULATORY SYSTEM

SHORT HALF LIFE HORMONES

• HORMONES WITH SHORT HALF LIVES INCREASE AND DECREASE RAPIDLY IN PLASMA

• WATER SOLUBLE HORMONES

LONG LIFE HORMONES

• HORMONES WITH LONG HALF LIVES HAVE RELATIVE STABLE LEVELS IN PLASMA

• STEROID HORMONES

FACTORS THAT INFLUENCE THE HALF LIFE OF HORMONES

• ELIMINATION– EXCRETION– METABOLISM– CONJUGATION– ACTIVE TRANSPORT

• CONSERVATION– PROTECTION FROM EXCRETION – PROTECTION FROM METABOLISM– PROTECTION BECAUSE OF HORMONE STRUCTURE

HORMONAL INTERACTIONS WITH TARGET CELLS

• HORMONES BIND TO TARGET CELL RECEPTORS

• ALTER RATE OF CELLULAR ACTIVITIESACTIVATE OR INACTIVATE

ENZYMESINCREASE OR DECREASE RATE OF

SYNTHESIS OF MOLECULES IN CELLSCAUSES CHANGES CELL MEMBRANE

PERMEABILITY

HORMONE RECEPTORS

• PROTEIN OR GLYCOPROTEIN

• EACH RECEPTOR HIGHLY SPECIFIC FOR ITS HORMONE

• A HORMONE MAY HAVE DIFFERENT RECEPTORS

• TARGET CELLS HAVE RECEPTORS-NONTARGET CELLS DO NOT

RECEPTORS AND DOWNREGULATION

• NUMBER OF RECEPTORS DECREASE AFTER EXPOSURE TO CERTAIN HORMONES

• RESPOND TO SHORT TERM INCREASES IN HORMONE CONCENTRATIONS

MECHANISMS OF DOWN REGULATION

• RECEPTOR SYNTHESIS DECREASES

• COMBINATION OF HORMONES AND RECEPTORS INCREASE RATE OF RECEPTOR MOLECULE DEGRADATION

RECEPTORS AND UP REGULATION

• SOME TISSUES EXHIBITG PERIODIC INCREASES IN SENSITIVITY TO CERTAIN HORMONES

• THE EXPOSURE OF A TISSUE TO ONE HORMONE INCREASES ITS SENSITIVITY TO ANOTHER

TYPES OF RECEPTORS

• MEMBRANE BOUND

• INTRACELLLULAR

MEMBRANE BOUND RECEPTORS

• WATER SOLUBLE HORMONES

• REVERSIBLE BINDING

• EQUILIBRIUM EXISTS

CHARACTERISTICS OF HOMONE RECEPTORS OF

THE CELL MEMBRANE

• GENERALLY LARGE MOLECULES

• ALMOST ALWAYS HIGHLY SPECIFIC FOR SINGLE HORMONE

• INACTIVE WHEN HORMONE IS NOT BOUND TO IT

EFFECT OF HORMONAL BINDING TO RECEPTORS

• SELDOM DIRECTLY AFFECT INTRACELLULAR MACHINERY

• BINDING USUALLY ACTIVATES CELLULAR PROCESSES

• SOMETIMES BINDING INACTIVATES CELLULAR PROCESSES

• DIRECT OR INDIRECT EFFECTS

DIRECT EFFECTS• CONFORMATIONAL CHANGE OF RECEPTOR

MOLECULE CHANGES MEMBRANE PERMEABILITY • ESPECIALLY SODIUM, CHLORIDE AND CALCIUM

IONS• ACETYLCHOLINE—a neurotransmitter• SEROTONIN---a hormone and neurotransmitter• GLYCINE—a neurotransmitter• GABA---a neurotransmitter• GROWTH HORMONE---a hormone

INDIRECT EFFECTS

• HORMONES THAT ACTIVATE G PROTEINS AND ALTER MEBRANE CHANNELS OR ACTIVATE INTRACELLULAR MEDIATORS

• HORMONES THAT ALTER ACTIVITY OF INTRACELLULAR ENZYMES TO CATALYZE SYNTHESIS OR PHOSPHORYLATION

HORMONES THAT ACTIVATE G PROTEINS

• OXYTOCIN• VASOPRESSIN• LUTEINIZING HORMONE• FOLLICLE STIMULATING

HORMONE• PROLACTIN• ATRIAL NATRIURETIC

HORMONE

• THYROID STIMULATING HORMONE

• PARATHYROID HORMONE

• GLUCAGON• EPINEPHRINE• ADRENOCORTICOTROPI

C HORMONE

EFFECTS OF HORMONE BINDING

• REGULATION OF MEMBRANE CHANNELS

• INCREASING OR DECREASING INTRACELLULAR MEDIATORS

c GMP & c AMP

HOW G PROTEINS REGULATE THE SYNTHESIS OF

INTRACELLULAR MEDIATORS

• G PROTEIN ALTERS ACTIVITY OF ENYZMES AT INNER SURFACE OF CELL MEMBRANE

ADENYL CYCLASE & GUANYL CYCLASE

• INCREASES OR DECREASES c AMP OR c GMP LEVELS IN CELL

Cyclic AMP AS AN INTRACELLULAR MEDIATOR

• PROTEIN AND POLYPEPTIDE HORMONESCTH, TSH, LH, FSH, ADH, PTH, GLUCAGON, CATECHOLAMINES, SECRETIN AND HYPOTHALAMIC RELEASING HORMONES

• ACT BY cyclic ADENOSINE MONOPHOSPHATE MECHANISM

ADENOSINE MONOPHOSPHATE SECOND MESSENGER SYSTEM

• HORMONE IS FIRST MESSENGER

• BINDS TO RECEPTOR ON OUTER SURFACE OF CELL MEMBRANE

• RECEPTOR ASSOCIATED A G PROTEIN

• SOME EXCITATORY-SOME INHIBITORY

FUNCTION OF ADENYLATE CYCLASE

• CONVERTS ATP TO cyclic AMP

ACTIVITY OF cyclic AMP

• ACTIVATES OTHER ENZYMES

• USUALLY IN AN ENZYME CASCADE

• JUST A FEW cyclic AMP MOLECULES CAN HAVE POWERFUL EFFECT

PROTEIN KINASES• ACTIVATED BY cyclic AMP• USE PHOSPHATES AND ENERGY FROM

ATP TO PHOSPHORYLATE ANOTHER ENZYME

• ACTIVATE OR INACTIVATE ENZYME• OFTEN ACTIVATION OF ENZYME IS THE

RATE LIMITING REACTION IN METABOLIC PATHWAY

• COMMON IN CELLS

EXCITATORY G PROTEINS

• ACTIVATES ADENYLATE CYCLASE

ACTION OF c AMP AND c GMP• ACTIVATING cyclic AMP or cyclic GMP

ACTIVATES PROTEIN KINASE/PHOSPHOKINASE

GLUCAGON EFFECTS ON LIVER CELLS

• ELEVATE cyclic AMP LEVELS

• ACTIVATE ENZYME SYSTEM

• PROMOTES BREAKDOWN OF GLYCOGEN INTO GLUCOSE

cyclic GUANOSINE MONOPHOSPHATESECOND MESSENGER SYSTEM• SOME CELLS USE INSTEAD OF cyclic

AMP

• ATRIAL NATRIURETIC HORMONE

• NITRIC OXIDE

INTRACELLULAR MEDIATOR MOLECULES WILL HAVE DIFFERENT

EFFECTS IN THE VARIOUS CELLS THAT USE THEM

•

G PROTEINS AND PHOSPOINOSITOL

• PHOSPHOLIPASE C

• ACTS ON PHOSPHOINOSITOL TO FORM DIACYLGLYCEROL & INOSITOL TRIPHOSPHATE

• INOSITOL TRIPHOSPHATE CAUSES RELEASE OF CALCIUM

• DIACYLGLYCEROL AND CALCIUM IONS ALTER ACTIVITY OF PROTEIN KINASES

ALTER CALCIUM PERMEABILITYALTER SYNTHESIS IN CELL

EFFECTS ON SMOOTH MUSCLE• IN RESPONSE TO EPINEPHRINE• INOSITOL TRIPHOSPHATE STIMULATES CALCIUM

RELEASE FROM ENDPLASMIC RETICULUM AND/OR CELL MEMBRANE

• CALCIUM BINDS WITH CALMODULIN• CALMODULIN BIND TO ENZYME THAT

PHOSPHORYLATES MYOSIN MOLECULES TO STIMULATE CONTRACTION

• DIACYLGLYCEROL REGULATES ENZYMES THAT REGULATE SYNTHESIS OF PROSTAGLANDINS

HORMONE RECEPTORS THAT DIRECTLY SYNTHESIZE AN

INTRACELLULAR MEDIATOR• ATRIAL NATRIURETIC HORMONE

BINDS WITH RECEPTOR• GUANYLYL CYCLASE ACTIVATED• PRODUCES cyclic GMP FROM GTP• cyclic GMP CAUSES INCREASED

EXCRETION OF SODIUM IONS• INCREASED WATER VOLUME IN

URINE

HORMONES THAT BIND TO RECEPTORS THAT

PHOSPHORYLATE INTRACELLULAR HORMONES• MEMBRANE BOUND RECEPTORS

• RECEPTOR ACTS AS PHOPHORYLASE ENCYME

• ATCHES PHOPHATE FROM ATPs TO RECPTOR AND INTRACELLULAR PROTEINS

• INSULIN

• GROWTH HORMONE,

CASCADE EFFECT

• FEW MEDIATOR MOLECULES ACTIVATE SEVERAL ENZYMES

• ACTIVATED ENZYMES ACTIVATE SEVERAL OTHER ENZYMES

INTRACELLULAR HORMONE

RECEPTORS • PROTEIN MOLECULES INSIDE CELL• SOME FLOAT IN CYTOPLASM• OTHERS IN NUCLEUS• HORMONES BIND TO INTRACELLULAR RECEPTORS CALLED

HORMONE RECEPTIVE ELEMENTS• SEX STEROID• MINERALOCORTICOIDS• GLUCOCORTICOIDS• THYROID HORMONE• VITAMIN D

STEROID HORMONES

• DIFFUSE ACROSS CELL MEMBRANE

• BINDS TO DINA SEMENTS CALLED HORMONE RESPONSIVE ELEMENTS

• TRIGGERS ACTIVATION OR INACTIVATION OF SPECIFC GENES

• ALTERS TRANSCRIPTION RATE

ALDOSTERONE• AFFECTS RENAL TUBULAR CELLS

• COMBINES WITH SPECIFIC RECEPTOR PROTEIN

• COMPLEX MOVES INTO NUCLEUS

• COMPLEX ACTIVATES SPECIFIC GENES

• m RNA IS FORMED AND DIFFUSES INTO CYTOPLASM

• TRANSLATION PRODUCES NEW PROTEINS

• PROTEINS PROMOTE SODIUM REABSORPTION INTO TUBULES AND SECRETION OF POTASSIUM INTO TUBULES

• TAKES FROM 45 MIN TO SEVERAL HOURS