intracellular messenger lecture notes

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
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DIRECT COMMUNICATION
SYNAPTIC COMMUNICATION
AUTOCRINE COMMUNICATION
PARACRINE COMMUNICATION
ENDOCRINE COMMUNICATION
– http://www.wisconline.com/objects/index_tj.asp?objid=AP137
04
DIRECT COMMUNICATION
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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
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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
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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
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• VASOPRESSIN
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• LUTEINIZING
HORMONE
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• FOLLICLE
STIMULATING
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HORMONE
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• 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
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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
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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