Pharmacological evidence for high affinity and low affinity a2-adrenoceptor binding sites in rat vas deferens

Differential antagonistic activity against imidazoline- and phenethylamine-induced inhibition of field stimulated rat vas deferens is described. Competitive antagonism of the imidazolines, chlonidine and B-HT 920, was produced by the a2-selective antagonists yohimbine and phentolamine, whereas, only partial antagonism of a-methyl noradrenaline and adrenaline was observed. Higher concentrations of yohimbine (above 2 microM) and phentolamine (above 20 microM) failed to produce a further shift in the dose-response curves of these agonists. The rate of recovery of the twitch response following clonidine- or B-HT 920-induced inhibition was very slow, even after repeated washing of the tissue. On the other hand recovery following a-methyl noradrenaline or adrenaline was extremely rapid. The present results provide pharmacological evidence in support of the previously proposed existence of high and low affinity binding site on the a2-adrenoceptor.