Acetylcholine-Induced Desensitization of Muscarinic Contractile Response in Guinea Pig Ileum Is Inhibited by Pertussis Toxin

We investigated the effects of pertussis toxin treatment on ace-tylcholine-induced desensitization of the muscarinic contractile response in guinea pig ileum. Incubation of the isolated ileum with acetylcholine (30 M) for 20 min caused a decrease in the sensi-tivity of the ileum to the contractile action of the muscarinic agonist oxotremorine-M. This desensitization was characterized by an increase in the EC50 value of oxotremorine-M without a change in its maximal effect. A maximal 4- to 5-fold increase in the EC50 value of oxotremorine-M was measured at the earliest time inves-tigated after acetylcholine treatment (5 min), and normal sensitivity recovered within approximately 20 min after washout of acetyl-choline. Treatment of the ileum with pertussis toxin caused a small increase in the contractile response to oxotremorine-M when measured without prior exposure to acetylcholine. After exposur