α1B-Adrenoceptor Subtype Mediating the Phenylephrine-Induced Contractile Response in Rabbit Corpus Cavernosum Penis

Abstract

The alpha 1-adrenoceptor subtype mediating contraction to phenylephrine in rabbit corpus cavernosum penis (CCP) was investigated using selective alpha 1-adrenoceptor subtype antagonists. WB4101 ((2-(2,6-dimethoxy-phenoxyethyl)-aminomethyl-1, 4-benzodioxane) hydrochloride), 5-methylurapidil and tamsulosin concentration-dependently produced a parallel rightward shift of the concentration-response curve to phenylephrine, yielding pKB values of 8.05, 7.59 and 9.21, respectively. The slopes of the Schild plots were not different from unity. These antagonists did not affect the maximum response to phenylephrine. Oxymetazoline (1 microM), which initially caused a small contraction, produced a parallel rightward shift of the concentration-response curve to phenylephrine with an apparent pKB value of 6.99. However, oxymetazoline seemed to act as a non-surmountable antagonist to the phenylephrine-induced contraction, reducing the maximum response by 71.1%. Chloroethylclonidine (25 and 100 microM) produced a parallel rightward shift of the concentration-response curve to phenylephrine without altering the maximum response. These results show that the alpha 1-adrenoceptor in rabbit CCP has a relatively low affinity for WB4101, 5-methylurapidil, tamsulosin and oxymetazoline and is sensitive to inactivation by chloroethylclonidine. It is suggested that the alpha 1-adrenoceptor subtype mediating contraction to phenylephrine in rabbit CCP has the characteristics of the alpha 1B-adrenoceptor subtype.