ELECTROCHEMICAL AND ELECTROPHYSIOLOGICAL ANALYSIS OF THE EFFECTS OF SK-AND-F-104078 ON PREJUNCTIONAL ALPHA-2-ADRENOCEPTORS

SK&F 104078 is proposed to be a selective postjunctional alpha-2-adrenoceptor antagonist. We examined its effects on the electrically evoked release of endogenous noradrenaline (NA) from the rat tail artery and of ATP from the mouse vas deferens, as determined electrochemically or by extracellular recording, respectively. The alpha-2-adrenoceptor antagonist yohimbine (0.1 and 1-mu-M) increased NA release at both 2 and 20 Hz; the effect of yohimbine was further enhanced by the NA uptake blocker cocaine. SK&F 104078 (0.01-1-mu-M) did not change NA release at 2 or 20 Hz in the absence or presence of cocaine. NA release at 2 Hz was dose dependently depressed by the alpha-2-adrenoceptor agonist xylazine, an effect reversed by yohimbine (1-mu-M) but unaffected by SK&F 104078 (0.1 and 1-mu-M). Similarly, the inhibitory effect of xylazine on ATP release at 0.1 Hz was not influenced by SK&F 104078 (1-mu-M) but partially reversed by yohimbine (1-mu-M). The results show (i) that prejunctional alpha-2-adrenoceptors mediate autoinhibition of the release of endogenous NA and ATP from sympathetic nerves in the rat tail artery and in the mouse vas deferens, respectively, and (ii) that SK&F 104078 does not block these receptors in the concentration range 0.01-1-mu-M.