The inhibition by dopamine of cholinergic transmission in the isolated guinea-pig ileum. Mediation through alpha-adrenoceptors.

1. Segments of the guinea-pig ileum were incubated in Tyrode's solution containing 3 microM propranolol. Dopamine, like noradrenaline and clonidine, inhibited the twitch response to field stimulation. The inhibitory action of dopamine remained unchanged in the presence of the dopamine uptake inhibitor nomifensine (1 microM). Tissue from reserpine-pretreated animals was insensitive to tyramine but the response to dopamine was not affected. It is, therefore, assumed that the effect of dopamine is due to a direct receptor stimulation and not to the release of noradrenaline. 2. The inhibitory action of dopamine was not antagonized by the dopamine receptor antagonists cis-flupenthixol, pimozide or domperidone. 3. Metoclopramide, sulpiride and tolazoline were competitive antagonists of the inhibitory effects of dopamine. The pA2-values for metoclopramide against dopamine (5.64), noradrenaline (5.52), and clonidine (5.57) did not differ significantly. Likewise, there was no significant difference between the pA2-values for sulpiride (5.30, 5.29, 5.50) and those for tolazoline (6.52, 6.69, 7.02) determined against dopamine, noradrenaline and clonidine. 4. Apomorphine inhibited the twitch response, and this inhibition was not affected by tolazoline, sulpiride or pimozide. 5. It is concluded that dopamine inhibits the twitch response in the guinea-pig ileum through stimulation of neuronal alpha-adrenoceptors. Metoclopramide and sulpiride are weak antagonists at these receptors. The results provide no evidence for the existence of specific inhibitory dopamine receptors in the guinea-pig ileum.