Involvement of enteric neurones in the response of guinea-pig ileum preparations to metoclopramide.

The role of myenteric neurones in mediating the stimulant effects of metoclopramide in vitro in the guinea-pig ileum has been investigated using the non-ionic surfactant Triton X-100. Histological examination of the ileum 30 days after application of Triton X-100 to the serosal surface demonstrated a marked reduction in the number of ganglion cells and nerve elements in the myenteric plexus. Longitudinal muscle-myenteric plexus (LM-MP) preparations from Triton X-100-treated animals were unresponsive to dimethylphenylpiperazinium and responded poorly or not at all to electrical field stimulation. Metoclopramide (30 microM) elicited small contractions in LM-MP preparations from control and sham-operated animals but failed to contract Triton X-100-treated tissues. However, tissues responded in a similar manner to exogenous acetylcholine (ACh). These results demonstrate the importance of a prejunctional site of action for metoclopramide in this tissue and suggest that contractile responses to the drug are mediated indirectly, probably by increased release of ACh from myenteric neurones.