Vasoactive intestinal polypeptide actions on the guinea pig intestinal mucosa during neural stimulation

Electrical stimulation of the mucosal innervation of the guinea pig ileum results in an increase in chloride secretion that is mediated in part by excitation of muscarinic cholinergic receptors on enterocytes. This study investigated the involvement of vasoactive intestinal peptide in the cholinergic and noncholinergic phases of the secretory response evoked by electrical stimulation of submucosal neurons in the guinea pig ileum. Flat sheets of ileum set up in Ussing flux chambers responded to exogenous vasoactive intestinal peptide by an increase in baseline short-circuit current which was reduced by furosemide and by vasoactive intestinal peptide antiserum. When submucosal neurons were electrically stimulated, a biphasic change in short-circuit current was evoked. Vasoactive intestinal peptide, forskolin, and isobutylmethylxanthine enhanced the cholinergic portion of the response, whereas the antiserum prevented or reduced the effects of the peptide but not of forskolin. In the presence of atropine to eliminate the cholinergically mediated response, vasoactive intestinal peptide reduced the noncholinergic phase of the response and its action was prevented by the antiserum. Vasoactive intestinal peptide enhanced the increase in short-circuit current evoked by the muscarinic agonist bethanechol. These results demonstrate that vasoactive intestinal peptide and other substances that stimulate secretion by increasing cyclic 3',5'-adenosine monophosphate levels in enterocytes potentiate the calcium-dependent, cholinergic phase of the chloride secretory response evoked by neural stimulation of the guinea pig ileum. No evidence was found for vasoactive intestinal peptide as the mediator of the noncholinergic phase of the response.