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.
J
J
Bou
A G
AG
Fernández
J M
JM
Jauregui
R
R
Massingham
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009197:Myenteric Plexus / Q000187:drug effects*; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology
D011092:Polyethylene Glycols; D004246:Dimethylphenylpiperazinium Iodide; D017830:Octoxynol; D008787:Metoclopramide; D000109:Acetylcholine