Alpha 2-adrenoceptor blockade prevents cardiac glycoside-evoked neurotransmitter release from sympathetic nerves in dog saphenous vein.
1 The effect of alpha-adrenoceptor antagonists upon neurotransmitter release evoked by cardiac glycosides from sympathetic nerve terminals has been investigated in dog saphenous vein. 2 In rings of saphenous vein preloaded with [3H]-noradrenaline, acetylstrophanthidin (ACS) caused a concentration-dependent efflux of 3H (EC50 ca. 4.4 microM) that was attenuated by phentolamine and yohimbine but not by prazosin. 3 In helical strips of saphenous vein superfused with ACS at EC50 the efflux of 3H-compounds in general, and of [3H]-noradrenaline in particular, occurred after a short delay and increased with time to a maximum reached at 75 min. Phentolamine and phenoxybenzamine, but not prazosin reduced the efflux of [3H]-noradrenaline and of total 3H-compounds throughout the time-course of the ACS-evoked effect. 4 In helical strips of saphenous vein the glycoside ouabain also caused an increase in [3H]-noradrenaline and in total 3H-efflux that was attenuated by phentolamine. 5 By contrast with the above, in bovine adrenal medullary chromaffin cells, which appear to have no functional alpha-adrenoceptors, ACS caused a small, but significant increase in 3H-efflux which was not prevented by phentolamine. 6 Phentolamine, at concentrations that attenuate markedly the ouabain- or ACS-evoked increase in 3H-efflux from dog saphenous vein, did not cause significant inhibition of cocaine-sensitive [3H]-noradrenaline uptake nor did it reduce the extent of the 3H-efflux evoked either by tyramine or by reduced extracellular Na+. These findings imply that phentolamine does not affect ACS-evoked neurotransmitter release by an action on the catecholamine uptake mechanism. 7. It is concluded that the cardiac glycoside-evoked increase in neurotransmitter release from noradrenergic nerve terminals ofdog saphenous vein is modulated by a mechanism that involves an alpha2- adrenoceptor.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002301:Cardiac Glycosides / Q000494:pharmacology*; D002417:Cattle; D002838:Chromaffin System / Q000187:drug effects; D004285:Dogs; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002301:Cardiac Glycosides; D018377:Neurotransmitter Agents; D013327:Strophanthidin; D000254:Sodium-Potassium-Exchanging ATPase; C004681:acetylstrophanthidin; D010646:Phentolamine