Different α1-adrenoceptor subtypes mediate contraction in rabbit aorta and urethra

Abstract

The α 1-adrenoceptor subtypes mediating contraction of rabbit aorta and urethra were pharmacologically characterized using an isolated organ bath technique. Although aorta was as sensitive as urethra to the contractile action of methoxamine, phenylephrine was about 10 times more potent as a contractile agonist on aorta than on urethra. In aorta, the rank order of agonist sensitivity was norepinephrine > phenylephrine > clonidine > methoxamine whereas the rank order in urethra was clonidine > methoxamine ≥ phenylephrinc > norepinephrine. A lack of significant correlation between the potency of different α 1-adrenoceptor antagonists tested against the phenylephrine-induced contraction in aorta and in urethra indicated that different α 1-adrenoceptor subtypes mediated the contractile response in the two preparations. The potency of different α 1-adrenoceptor antagonists tested in rabbit urethra was significantly correlated with their affinity for the cloned human α 1c-, but not α 1a- or α 1b-, adrenoceptor subtype. Such a clear correlation with the potency of different α 1-adrenoceptor antagonists tested in rabbit aorta and their affinity for one subtype of cloned human α 1-adrenoceptor was not found. Chlorethylclonidine, which produced a 10 000-fold rightward shift in the phenylephrine concentration-response curve for rat aorta, had a weak inhibitory effect in rabbit aorta and urethra as well as in other rabbit tissues (spleen, fundus, renal artery, saphenous artery). The results indicate that significant heterogeneity exists among α 1-adrenoceptor in rabbit aorta and urethra ( α 1c-adrenoceptor). However, chlorethylclonidine does not seem to be a suitable tool for the differentiation of α 1-adrenoceptor subtypes in the rabbit.