Domperidone improves myogenically transmitted antroduodenal coordination by blocking dopaminergic receptor sites

An intact guinea-pig gastroduodenal preparation was used to determine the mechanism by which antroduodenal coordination is inhibited by dopamine and improved by domperidone. Domperidone effectively antagonised the inhibitory effects of dopamine in a competitive way. The lack of interference of alpha 1-, alpha 2-, and beta- adrenergic antagonists on the dopaminergic modulation indicates the presence of specific dopamine receptors in the gut wall. Both tetrodotoxin and atropine, but not hexamethonium, prevented the stimulatory effects of domperidone, indicating that intact (postganglionic?) cholinergic intramural nerves were a prerequisite for detecting these effects. In the presence of tetrodotoxin, bethanechol induced coordinated motor patterns, revealing the myogenic control of antroduodenal coordination. When dopamine was tested on coordinated motor patterns as induced by the combination of bethanechol and tetrodotoxin, it no longer inhibited coordination, suggesting that the dopamine receptor is located on nervous structures. It was concluded that dopamine inhibited, and domperidone effectively improved, myogenically controlled antroduodenal coordination via specific dopamine receptors located on nervous structures in the gut wall of the guinea-pig.