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

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Abstract
Catecholamine control of circular smooth muscle activity of the lower oesophageal (LOS) and pyloric sphincters (PS) of the guinea-pig was studied using α- and β-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 α- and β-adrenoceptor antagonists, phentolamine and propranolol, indicated that contractions of both sphincters by NA and DA involved an α-type adrenoceptor whilst relaxation was mediated via a β-adrenoceptor (PS) or via both α- and β-adrenoceptors (LOS). Use of the α1 and α2 antagonists, prazosin and yohimbine, indicated that the α-adrenoceptor type involved with both the contractions and relaxation was α1. 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 α1-adrenoceptors was therefore concluded. In selectively antagonizing the contractile effects of DA in the PS, domperidone enhanced DA's ability to relax this sphincter.