Different sites of action for alpha 2-adrenoceptor antagonists in the modulation of noradrenaline release and contraction response in the vas deferens of the rat.

Abstract

Rat vas deferens was prepared, loaded with [3H]noradrenaline, and superfused to measure the release of tritium in resting conditions and in response to electrical field stimulation. The alpha 2-adrenoceptor antagonists yohimbine, CH-38083 (7,8-(methylenedioxi)-14 alpha-hydroxyalloberbane HCl), and idazoxan increased the electrically induced release of tritium in a concentration-dependent manner, whereas noradrenaline and the alpha 2-adrenoceptor agonist xylazine exerted opposite effects. The inhibitory effect of noradrenaline on electrically induced tritium release was antagonized by yohimbine, CH-38083, and idazoxan. Of the alpha 2-adrenoceptor antagonists tested, yohimbine and CH-38083 reversed the xylazine-induced inhibition of tritium release, and idazoxan was found to be completely ineffective against xylazine. Idazoxan, yohimbine and CH-38083 antagonized the inhibitory effect of xylazine on electrical stimulation-induced contractions of the vas deferens, as was evidenced by the apparent pA2 values. We conclude from the present experiments that noradrenaline and xylazine inhibit noradrenaline release by acting on distinct prejunctional alpha 2-adrenoceptors and that the receptor subtype that responds to xylazine is insensitive to idazoxan. In addition, inhibition by xylazine of contractility but not of noradrenaline release was antagonized by idazoxan, suggesting that besides noradrenergic neurotransmission, other motor transmitter systems (purinergic) may also be involved in the inhibition by alpha 2-adrenoceptor antagonists of mechanical responses in the rat vas deferens.