The mechanism of alpha-adrenergic inhibition of catecholamine release.
1 The effect of alpha-adrenoceptor agonists on membrane adenosine triphosphatase (ATPase) activity was studied in membranes from the bovine adrenal medulla and the rat submaxillary gland. 2 alpha-Adrenoceptor agonists (10(-7) to 10(-5) M) enhanced significantly Na,K-ATPase activity but not Mg-ATPase activity in adrenal medulla. This effect was not observed in membranes from phaeochromyocytoma. Phenylephrine (10(-5) M), naphazoline (10(-5) M) and clonidine (10(-5) M) caused a significant increase of the activity of Na,K-ATPase (but not of Mg-ATPase) in the submaxillary gland. The enhancement became more prominent after ligature of the submaxillary duct but disappeared completely after superior cervical ganglionectomy. Thus, the effect of the alpha-adrenoceptor agonists was due to an action on adrenergic nerve terminals in the submaxillary gland. 3 Phenylephrine and naphazoline did not affect 45Ca uptake but enhanced the rate of 45Ca efflux from adrenal medullary slices in vitro. 4 Phenylephrine enhanced the rate of 45Ca efflux from slices of submaxillary gland (with previous ligation of the duct); this was blocked by phentolamine and sympathetic denervation. Therefore phenylephrine was acting on the adrenergic nerve terminals. 5 It is suggested that the inhibition by alpha-adrenoceptor agonists of the exocytotic release of catecholamines from adrenergic nerve terminals and from chromaffin cells may be due to activation of the sodium pump, which results in enhancement of calcium efflux, causing a reduction of free intracellular Ca2+.
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000313:Adrenal Medulla / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009374:Neoplasms, Experimental / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D002395:Catecholamines; D010656:Phenylephrine; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D009638:Norepinephrine