INDUCTION OF ILEUM MUSCARINIC CHOLINOCEPTOR SIGNAL-TRANSDUCTION PATHWAYS BY RAT INTERFERON-GAMMA

We have recently shown that rat interferon-gamma (IFN gamma) can trigg er a cholinergic muscarinic response upon interaction with isolated ra t atria, decreasing both the contractile tension and cAMP synthesis, a nd increasing cGMP production. Because the intestine is rich in cholin ergic muscarinic receptors, and IFN gamma-producing cells are normal c omponents of the mucosal immune system, we investigated whether IFN ga mma could also modulate the muscarinic cholinergic activity of the int estine. Our results indicate that IFN gamma may interact with ileum ch olinergic muscarinic receptors by inhibiting binding of the radiolabel led antagonist quinuclidinyl benzylate (H-3-QNB), decreasing cAMP form ation and increasing cGMP synthesis. These effects are associated with increased mechanical activity of the isolated ileum strips, and can b e blunted by pretreatment of the tissue with atropine.