ALPHA-2-ADRENOCEPTOR-MEDIATED MODULATION OF THE NITRERGIC INNERVATION OF THE CANINE ISOLATED ILEOCOLONIC JUNCTION

1 The effects of specific alpha-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. 2 During a substance P-induced contraction and in the presence of atropine and guanethidine, the specific alpha1-adrenoceptor agonist, phenylephrine and antagonist, prazosin, as well as the specific alpha2-adrenoceptor antagonist, yohimbine, had no effect on the NANC relaxations evoked by electrical field stimulation. In contrast, clonidine and the more specific alpha2-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. 3 During a noradrenaline-induced contraction, clonidine, but not UK-14,304 significantly augmented the relaxations to electrical stimulation. 4 The adrenoceptor agonists and antagonists used had no effect on concentration-response curves to NO or on the relaxation induced by nitroglycerin. 5 These results indicate that stimulation of prejunctional alpha2-adrenoceptors inhibits the nitrergic NANC relaxations induced by field stimulation and thus suggest prejunctional regulation of nitric oxide release via alpha2-adrenoceptors in the canine ileocolonic junction.