Pharmacological and electrophysiological discrimination of contractile responses to selective alpha 1- and alpha 2-adrenoceptor agonists in rat tail artery

Abstract

Pharmacological and electrophysiological properties of postsynaptic alpha-adrenoceptor subtypes in rat tail artery were compared using selective alpha 1- and alpha 2-adrenoceptor agonists. Five alpha-adrenoceptor agonists contracted the tail artery with the following order of maximal effects: norepinephrine (alpha 1 and alpha 2) greater than methoxamine (alpha 1) = phenylephrine (alpha 1) much greater than clonidine (alpha 2) greater than UK-14,304 (alpha 2). Phenoxybenzamine greatly diminished contractions induced by methoxamine and phenylephrine, but had little effect on responses to UK-14,304. Idazoxan antagonized more potently against UK-14,304 than against methoxamine. These results suggest the heterogeneity of postsynaptic alpha-adrenoceptors in the rat tail artery. Furthermore, responses to methoxamine and phenylephrine 1) had faster onsets and 2) were more resistant to Ca2+ entry blockers, nicardipine and diltiazem, and a promotor, Bay K 8644, or decreasing of extracellular Ca2+ and 3) were more sensitive to a calmodulin antagonist, W-7, than the responses to UK-14,304 and clonidine. Both methoxamine and UK-14,304 depolarized the membrane but methoxamine produced stronger depolarization than UK-14,304. Therefore, the high sensitivity of alpha 2-adrenoceptor agonists-induced responses to Ca2+ entry blockers and promotors cannot be accounted for solely by membrane depolarization. These results may indicate the differences in the Ca2+ movement for the contractions produced by alpha 1- and alpha 2-adrenoceptor agonists.