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

Publisher Website
Google Scholar
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) > methoxamine (.alpha.1) = phenylephrine (.alpha.1) .mchgt. clonidine (.alpha.2) > 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 promoter. 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 sensitive of .alpha.2-adrenoceptor agonists-induced responses to Ca2+ entry blockers and promoters 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.