ANALYSIS OF AGONISM AT FUNCTIONAL PREJUNCTIONAL ALPHA(2)-ADRENOCEPTORS OF RAT VAS-DEFERENS USING OPERATIONAL AND NULL APPROACHES

The alpha(2)-adrenoceptors located prejunctionally on the postganglion ic neurons that innervate the smooth muscle of the prostatic portion o f the rat vas deferens were examined. For this purpose, three imidazol idine derivatives (structurally related to clonidine) were studied for their effects on twitch contractions elicited by electrical field sti mulation of this tissue. In this study, operational model-fitting and the nested hyperbolic method were used to analyse the effects of irrev ersible receptor alkylation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroqu inoline (EEDQ) on the alpha(2)-adrenoceptor-mediated effects of clonid ine (2-[2,6-dichlorophenylimino]imidazolidine) in stimulated vas defer ens. The operational model provided an estimate of K-A for clonidine w hich was not significantly different from the estimate obtained by usi ng the nested hyperbolic method (null approach). The data indicate a l arge receptor reserve at prejunctional alpha(2)-adrenoceptors for clon idine. The estimates of apparent affinity for St-587 2-chloro-5-triflu oromethylphenylimino]imidazoline) and St-591 (2-[2-chloro-5-methylphen ylimino]imidazolidine) did not depend on the method of calculation as the 'null' method and the 'operational' method gave similar answers. F urther, estimates of the ratio of tau values for these partial agonist s with respect to clonidine were numerically the same as those of thei r relative efficacies. Therefore, no limitations in the ability of the operational model to fit experimental data and provide reproducible e stimates of affinity and efficacy have been revealed for agonists acti ng at prejunctional alpha(2)-adrenoceptors.