On the ability of domperidone to selectively inhibit catecholamine-induced relaxation of circular smooth muscle of guinea-pig stomach

Abstract

Abstract The effects of noradrenaline and dopamine, and their interactions with α- and β-adrenoceptor antagonists and with domperidone, were studied on circular smooth muscle strips taken from the cardia, fundus, body and antrum of the guinea-pig stomach. Noradrenaline and dopamine caused relaxations of all tissues which were generally susceptible to antagonism by either propranolol or phentolamine in concentrations shown to antagonize the relaxations caused by isoprenaline or phenylephrine respectively. In addition, dopamine, in concentrations subthreshold for relaxation, caused contraction of the muscle strips which increased in intensity from the cardia to the antral region: these contractions were antagonized by phentolamine and yohimbine but were insensitive to prazosin: prazosin selectively inhibited the phenylephrine relaxations. With the exception of a modest reduction in the responses of the cardia to dopamine, all tissue responses to noradrenaline and dopamine were resistant to reserpine. Domperidone and haloperidol were found to selectively inhibit the phenylephrine- noradrenaline- and dopamine-induced relaxations of the stomach strips and to enhance the contractile component of dopamine's action: this ability of domperidone to facilitate a dopamine induced contraction, which was most marked in the body and antral regions, was prevented by phentolamine. It is thus concluded that domperidone antagonizes noradrenaline- and dopamine-induced relaxations at one adrenoceptor site having characteristics conistent with an α1-adrenoceptor type whilst failing to antagonize at a further dopamine-sensitive adrenoceptor site involved in contraction of circular smooth muscle of the stomach and having characteristics consistent with an α2-adrenoceptor.