MECHANISMS OF INTERCELLULAR COMMUNICATION INTERNET RESOURCES • http://www.vivo.colostate.edu/hbooks/path phys/endocrine/index.html • http://www.uri.edu/pharmacy/animation/hu angAnim.htm • http://www.infochembio.ethz.ch/links/en/bi ochem_hormone.html • http://www.scientia.org/cadonline/Biology/e ndocrine/action.ASP TYPES OF INTERCELLULAR COMMUNICATION • • • • • DIRECT COMMUNICATION SYNAPTIC COMMUNICATION AUTOCRINE COMMUNICATION PARACRINE COMMUNICATION ENDOCRINE COMMUNICATION – http://www.wisconline.com/objects/index_tj.asp?objid=AP137 04 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 • FREQUENCYMODULATED SIGNALS • FASTER ACTING • SHORT DURATION • GENERALLY LESS DISTRIBUTED ENDOCRINE • AMPLITUDEMODULATED 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 ACTIVITIES ACTIVATE OR INACTIVATE ENZYMES INCREASE OR DECREASE RATE OF SYNTHESIS OF MOLECULES IN CELLS CAUSES 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 RECEPTORSNONTARGET 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 HORMONES CTH, 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 MONOPHOSPHATE SECOND 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 PERMEABILITY ALTER 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 • MEMBRANEHORMONES 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