Pharmacological evidence that different a1 adrenoceptor subtypes mediate contraction in rabbit prostate and hypogastric artery

The α1-adrenoceptor subtypes mediating contraction of rabbit prostate and hypogastric artery were pharmacologically characterized using an isolated organ bath technique. The prostate had the same sensitivity to the contractile action of methoxamine and phenylephrine, whereas the hypogastric artery was five times less sensitive to the action of methoxamine in comparison with phenylephrine. Clonidine elicited contraction in the hypogastric artery but not in the prostate. BMY7378 was about 70-fold more potent to antagonize the phenylephrine-induced contraction in the hypogastric artery (pA2 8.14) than in the prostate (pA2 6.28), and 5-methyl-urapidil was about three-fold more potent on prostrate than on hypogastric artery. The potency of different α1-adrenoceptor antagonists tested in the rabbit prostate was significantly correlated with their binding affinity for the expressed recombinant α1A-, but not α1B- or α1D-, adrenoceptor subtype, whereas, the potency of the α1-adrenoceptor antagonists tested in the rabbit hypogastric artery was better correlated with the defined α1D-adrenoceptor. Chloroethylclonidine produced a 10-fold rightward shift in the phenylephrine concentration–response curve in the hypogastric artery but only had a weak effect in the prostate. The results indicate that significant heterogeneity exists among α1-adrenoceptor in the rabbit hypogastric artery (α1D-adrenoceptor) and the prostate (α1A-adrenoceptor).