Subtyping of alpha1-adrenoceptors responsible for the contractile response in the rat corpus cavernosum.
The subtyping of alpha1-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-1,4-benzodioxane (WB4101), a specific antagonist for alpha1A-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 alpha1A-adrenoceptors are responsible for the methoxamine-induced contraction of the rat cavernosal smooth muscle.
Tong
Y C
YC
Department of Urology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan, ROC.
Cheng
J T
JT
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010413:Penis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine