Hormones of the Adrenal Medulla 1-13
Transcript of Hormones of the Adrenal Medulla 1-13
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HORMONES OF THE
ADRENAL MEDULLA
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The adrenal medulla is an extension of the
sympathetic nervous system
While not necessary to life, they are
required for stress adaptation
Products are the catecholamines
(dopamine, epinephrine, norepinephrine)
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SYNTHESIS OF CATECHOLAMINES
1. Ring hydroxylation
Tetrahydropteridine iscofactor
Rate-limiting step in
catecholamine biosynthesis Competitive inhibition by -
methyltyrosine removal of
cofactor
phenylethanolamine-N
-methyltransferase
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SYNTHESIS OF CATECHOLAMINES
2. Decarboxylation
Needs pyridoxal phosphate Alpha-methyldopa is
competitive inhibitor (used in
the treatment ofhypertension)
phenylethanolamine-N
-methyltransferase
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SYNTHESIS OF CATECHOLAMINES
3. Side chain hydroxylation by a
mixed function oxidase Ascorbic acid is electron
donor Copper is at the active site
while fumarate acts as amodulator
4. N-methylation
PNMT is induced byglucocorticoids (e.g. duringstress response
phenylethanolamine-N
-methyltransferase
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Catecholamines cannot cross the blood-
brain barrier (so L-Dopa is given in
Parkinsons disease) 80% of catecholamines in medulla is
epinephrine
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(500 D)
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CATECHOLAMINE RELEASE
Calcium-dependent
Neural stimulation causes fusion of
storage granules with the plasmamembrane
Stimulated by cholinergic and -
adrenergic agents and inhibited by -adrenergic agents
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CATECHOLAMINE RELEASE
The adrenal medulla, unlike sympathetic
nerves, has no ability to reuptake
discharged catecholamines Half-life: 10-30 secs
Loosely associated with albumin
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Catechol-O-Methyltransferase
Monoamine oxidase
VMA
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dihydropteridine reductase
tyrosine hydroxylase
Dihydroxyphenyl
acetic acid
(VMA)
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MAO inhibitors are used to treat
hypertension and depression
VMA is elevated in patients with tumors ofthe adrenal medulla (Pheochromocytoma)
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CATECHOLAMINE RECEPTORS
1- increase glycogenolysis, smooth musclecontraction
2- smooth muscle relaxation,vasoconstriction
inhibits lipolysis, renin, insulin, platelet
aggregation
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CATECHOLAMINE RECEPTORS
1 increase lipolysis,increase force and rate ofheart contraction
2 increase hepatic gluconeogenesis andglycogenolysis
increase release of insulin and glucagon
relaxes smooth muscles
Beta receptor genes have no introns and arehomologous to rhodopsin (visual responseprotein)
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CATECHOLAMINE RECEPTORS Epinephrine activates alpha and beta receptors
Norepinephrine primarily binds to alpha receptors at
physiologic concentrations
Alpha and beta receptors are G-protein-linked Hormones that bind beta receptors activate adenylate
cyclase, while 2 receptors inhibit adenylate cyclase
1 receptors are coupled to processes that alter
intracellular calcium concentrations or modifyphosphatidylinositide metabolism