Catecholamine-induced relaxation and contraction of the lower oesophageal and pyloric sphincters of guinea-pig stomach: modification by domperidone

Abstract

Catecholamine control of circular smooth muscle activity of the lower oesophageal (LOS) and pyloric sphincters (PS) of the guinea-pig was studied using alpha- and beta-adrenoceptor agonists and antagonists. In both sphincters dopamine (DA) and noradrenaline (NA) caused relaxation followed by contraction of the circular smooth muscle, although the ability of NA to contract the PS was weak and inconsistent. Isoprenaline relaxed both sphincter preparations but, whilst phenylephrine contracted the muscle of the PS, it caused a biphasic relaxation-contraction of the LOS. The use of the alpha- and beta-adrenoceptor antagonists, phentolamine and propranolol, indicated that contractions of both sphincters by NA and DA involved an alpha-type adrenoceptor whilst relaxation was mediated via a beta-adrenoceptor (PS) or via both alpha- and beta-adrenoceptors (LOS). Use of the alpha 1 and alpha 2 antagonists, prazosin and yohimbine, indicated that the alpha-adrenoceptor type involved with both the contractions and relaxation was alpha 1. Both domperidone and haloperidol antagonized the contractile responses of both tissues to DA (and partly the relaxation of the LOS) but were similarly effective against the contractions induced by NA and phenylephrine; an effect on alpha 1-adrenoceptors was therefore, concluded. In selectively antagonizing the contractile effects of DA in the PS, domperidone enhanced DA's ability to relax this sphincter.