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Hormones of the Adrenal Medulla 1-13

Hormones of the Adrenal Medulla 1-13

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Published by: abstabs on Jan 16, 2010
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03/25/2012

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HORMONES OF THE ADRENAL MEDULLA

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)

SYNTHESIS OF CATECHOLAMINES
1

2

3

1. Ring hydroxylation  Tetrahydropteridine is cofactor  Rate-limiting step in catecholamine biosynthesis  Competitive inhibition by α methyltyrosine removal of cofactor
phenylethanolamine-N -methyltransferase

4

SYNTHESIS OF CATECHOLAMINES
2.
1

 

2

Decarboxylation Needs pyridoxal phosphate Alpha-methyldopa is competitive inhibitor (used in the treatment of hypertension)

3

4

phenylethanolamine-N -methyltransferase

SYNTHESIS OF CATECHOLAMINES
3.
1

 

2

3

4. 

4

phenylethanolamine-N -methyltransferase

Side chain hydroxylation by a mixed function oxidase Ascorbic acid is electron donor Copper is at the active site while fumarate acts as a modulator N-methylation PNMT is induced by glucocorticoids (e.g. during stress response

Catecholamines cannot cross the bloodbrain barrier (so L-Dopa is given in Parkinson’s disease)  80% of catecholamines in medulla is epinephrine

(500 D)

CATECHOLAMINE RELEASE
Calcium-dependent  Neural stimulation causes fusion of storage granules with the plasma membrane  Stimulated by cholinergic and β adrenergic agents and inhibited by α adrenergic agents

CATECHOLAMINE RELEASE
The adrenal medulla, unlike sympathetic nerves, has no ability to reuptake discharged catecholamines  Half-life: 10-30 secs  Loosely associated with albumin

Catechol-O-Methyltransferase

Monoamine oxidase

VMA

dihydropteridine reductase

tyrosine hydroxylase

Dihydroxyphenyl acetic acid

(VMA)

MAO inhibitors are used to treat hypertension and depression  VMA is elevated in patients with tumors of the adrenal medulla (Pheochromocytoma)

CATECHOLAMINE RECEPTORS
α 1- increase glycogenolysis, smooth muscle contraction α 2- smooth muscle relaxation, vasoconstriction inhibits lipolysis, renin, insulin, platelet aggregation

CATECHOLAMINE RECEPTORS
β 1 – increase lipolysis,increase force and rate of heart contraction β 2 – increase hepatic gluconeogenesis and glycogenolysis increase release of insulin and glucagon relaxes smooth muscles Beta receptor genes have no introns and are homologous to rhodopsin (visual response protein)

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 α 2 receptors inhibit adenylate cyclase α 1 receptors are coupled to processes that alter intracellular calcium concentrations or modify phosphatidylinositide metabolism

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