In vivo signal-transduction pathways to stimulate phasic contractions in normal and inflamed ileum

We investigated the in vivo signal-transduction pathways to stimulate phasic contractions in normal and inflamed ileum by close intra-arterial infusions of test substances. Methacholine stimulated phasic contractions dose dependently. This response was suppressed during inflammation. Verapamil inhibited the response to methacholine dose dependently in both normal and inflamed ileum. Neomycin inhibited the response partially in normal ileum and almost completely in inflamed ileum. H-7 and chelerythrine partially inhibited the methacholine response in normal ileum but had no significant effect in inflamed ileum. Ryanodine stimulated phasic contractions that were blocked by TTX, hexamethonium, atropine, or ruthenium red. Ruthenium red, however, had no significant effect on the contractile response to methacholine. Conclusions: 1) Ca²⁺ influx through the L-type channels may be the primary source of Ca²⁺ to stimulate in vivo phasic contractions. 2) Phosphatidylinositol hydrolysis enhances the stimulation of in vivo phasic contractions in the normal ileum. In the inflamed ileum, phosphatidylinositol hydrolysis may be essential to stimulate phasic contractions. 3) Inflammation may downregulate the protein kinase C pathway. 4) Ryanodine stimulates phasic contractions by the release of ACh.