Katsuo Furukawa (1), Russell Chess-Williams (2) and Toshimitsu Uchiyama (1)
(1) Department of Pharmacology, Toho University School of Medicine, Omori-nishi 5-21-16, Ota-ku, Tokyo 143, Japan (2) Department of Biomedical Science, School of Biological Sciences, University of Sheffield, Western Bank, Sheffield S10 2TN, U.K.
Abstract: The alpha1-adrenoceptor subtype mediating contraction to phenylephrine in rabbit corpus cavernosum penis (CCP) was investigated using selective alpha1-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 alpha1-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 alpha1-adrenoceptor subtype mediating contraction to phenylephrine in rabbit CCP has the characteristics of the alpha1B-adrenoceptor subtype.
Keywords:
Corpus cavernosum penis (rabbit), alpha1B-Adrenoceptor subtype, Phenylephrine, WB4101,
5-Methylurapidil