The effects of various pharmacological agents on the metoclopramide-induced increase in cholinergic-mediated contractions of rat isolated forestomach.

In longitudinal muscle strips of rat forestomach, metoclopramide (Mcp) increased the height of cholinergic-mediated contractions evoked by electrical field stimulation, probably by facilitating the release of neuronal acetylcholine. This response to Mcp was not prevented by drugs which blocked the synthesis of prostanoids or the actions of nicotine, morphine, noradrenaline, histamine and substance P. An involvement of dopamine in the mechanism of the response to Mcp was also excluded. Tachyphylaxis with 5-hydroxytryptamine (5HT) increased the electrically-evoked contractions and prevented the response to Mcp. Of the 5HT antagonists tested, only high concentrations of methysergide or phenylbiguanide reduced the ability of Mcp to increase the cholinergic-mediated contractions. These experiments are discussed in relation to the possibility that Mcp may increase neuronal ACh release in the gut by affecting 5HT synthesis or by acting on 5HT receptors.