Coupling between the beta-adrenergic receptor and the adenylate cyclase--pathophysiological implications.
Most beta-adrenergic effects are mediated by activation of the enzyme adenylate cyclase. Hormone binds to the receptor leading to an accelarated binding of GTP to the coupling protein, the N-protein, which is activated. This causes an activation of the adenylate cyclase and an increased formation of cAMP, the intracellular second messenger. The same principles hold good for other hormones coupled to adenylate cyclase. The sensitivity of the adenylate cyclase may be altered in different clinical and experimental conditions. An increased sensitivity is seen in hyperthyroidism in man and in the rat, and during starvation in rats. A decreased sensitivity is seen in hypothyroidism, in patients with pheochromocytoma, pseudohypoparathyroidism type I or multiple symmetric lipomatosis. Several reasons for the altered sensitivity have been suggested. The number of hormone receptors, the coupling between receptor and N-protein, the amount or function of the N-protein or the PDE activity may all vary in different conditions.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008066:Lipolysis / Q000187:drug effects; D008068:Lipomatosis / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism; D010908:Pituitary Hormones, Anterior / Q000494:pharmacology; D011547:Pseudohypoparathyroidism / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013959:Thyroid Diseases / Q000378:metabolism; D013963:Thyroid Hormones / Q000494:pharmacology
D002395:Catecholamines; D010908:Pituitary Hormones, Anterior; D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D013963:Thyroid Hormones; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases