Subtyping of α₁-adrenoceptors responsible for the contractile response in the rat corpus cavernosum

The subtyping of α₁-adrenoceptors responsible for mediating contraction in isolated corpus cavernosum of mature male Wistar rats was studied pharmacologically. Concentration-response studies of the cavernosal smooth muscle to three agonists: methoxamine, norepinephrine and octopamine showed that methoxamine exhibited the highest potency in inducing contractile response; the respective pD₂ values were: 6.22, 5.83 and 5.38. In the presence of 2-(2,6-dimethoxyphenoxyethyl)aminomethyl (WB4101), a specific antagonist for α(1A)-adrenoceptors, a parallel rightward shift of the concentration-response curve to methoxamine was observed. On the other hand, chloroethylclonidine (CEC) caused a rightward shift of the concentration-response curve to methoxamine with significant suppression of the maximum response. The pA₂ value for WB4101 obtained from Schild plot was 9.03 ± 0.06 with slope (95% CL) equal to 0.955 (1.088-0.832). In the absence of extracellular calcium ions, the methoxamine-induced contraction was reduced by 92%. Ca²⁺-Channel blockers, nifedipine 10^-6 M and diltazem 10^-6 M decreased the contractile response by 18 and 23%, respectively. The present findings suggest that α(1A)-adrenoceptors are responsible for the methoxamine-induced contraction of the rat cavernosal smooth muscle.