Pharmacological and Electrophysiological Discrimination of Contractile Responses to Selective _α1- and _α2-Adrenoceptor Agonists in Rat Tail Artery

抄録

Pharmacological and electrophysiological properties of postsynaptic α-adrenoceptor subtypes in rat tail artery were compared using selective α₁ and α₂-adrenoceptor agonists. Five α-adrenoceptor agonists contracted the tail artery with the following order of maximal effects: norepinephrine (α₁ and α₂)>methoxamine (α₁)=phenylephrine (α₁)>>clonidine (α₂)>UK-14, 304 (α₂). 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 α-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 α₂-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 α₁- and α₂-adrenoceptor agonists.