Involvement of M1 cholinergic receptors and enteric nerves in the spasmogenic activity of bacterial N-formyl oligopeptides on guinea-pig ileum.

Abstract

Bacterial N-formyl-methionyl oligopeptides are spasmogenic for guinea-pig ileum in vitro but the mechanism of this effect is not understood. To investigate this phenomenon further, we have determined pA2 values (the negative logarithm of the concentration of an antagonist reducing a double-dose agonist response to a single-dose response) for a number of potential antagonists of N-formyl-met-leu-phe (F-met-leu-phe) using histamine, acetylcholine, 5HT and substance P as control agonists. Atropine, pirenzepine and tetrodotoxin were potent inhibitors of F-met-leu-phe induced contraction (pA2's 8.4, 8.0 and 7.9, respectively) suggesting involvement of neural and cholinergic pathways in the response. Sulphasalazine, known to block the F-met-leu-phe receptor on neutrophil leucocytes, was also a potent inhibitor. Tachyphylaxis induced by either 5HT, or substance P, did not diminish the response to F-met-leu-phe, suggesting that these potential mediators were not involved. These studies indicate that bacterially synthesized formyl-methionyl oligopeptides bind to cells bearing receptors in guinea-pig ileum and produce muscle contraction via enteric cholinergic (M1) neural pathways.