α 2‐Adrenoceptor‐mediated modulation of the nitrergic innervation of the canine isolated ileocolonic junction

Abstract

The effects of specific α‐adrenoceptor agonists and antagonists on electrically‐evoked non‐adrenergic non‐cholinergic (NANC) relaxations, previously demonstrated as nitrergic, were investigated in isolated circular muscle strips of the canine ileocolonic junction. During a substance P‐induced contraction and in the presence of atropine and guanethidine, the specific α1‐adrenoceptor agonist, phenylephrine and antagonist, prazosin, as well as the specific α2‐adrenoceptor antagonist, yohimbine, had no effect on the NANC relaxations evoked by electrical field stimulation. In contrast, clonidine and the more specific α2‐adrenoceptor agonist, UK‐14,304, significantly reduced the electrically‐induced relaxations, preferentially those in response to low frequency stimulation. The inhibitory effect of UK‐14,304 on these relaxations was antagonized by yohimbine. During a noradrenaline‐induced contraction, clonidine, but not UK‐14,304 significantly augmented the relaxations to electrical stimulation. The adrenoceptor agonists and antagonists used had no effect on concentration‐response curves to NO or on the relaxation induced by nitroglycerin. These results indicate that stimulation of prejunctional α2‐adrenoceptors inhibits the nitrergic NANC relaxations induced by field stimulation and thus suggest prejunctional regulation of nitric oxide release via α2‐adrenoceptors in the canine ileocolonic junction. 1993 British Pharmacological Society