Role of muscarinic M 2 and M 3 receptors in guinea-pig trachea: effects of receptor alkylation

Abstract

Muscarinic M 2 receptors account for more than half the muscarinic receptor population in smooth muscles of a number of species and yet it is the smaller M 3 receptor population that mediates contraction of many of these tissues. The role of the majority of M 2 receptors in the control of smooth muscle tone is unclear. In guinea-pig ileal smooth muscle, an indirect contractile role (re-contraction) for M 2 receptors has been demonstrated in tissues subjected to M 3 receptor alkylation and stimulation of adenylyl cyclase. The present studies have employed the technique of irreversible receptor alkylation in order to investigate the role of muscarinic M 2 and M 3 receptors in the control of guinea-pig tracheal smooth muscle tone. Experiments were performed to determine (i) whether an indirect contractile role for M 2 receptors can be demonstrated in tracheal smooth muscle as described for ileum, and (ii) whether stimulation of M 2 receptors can inhibit isoprenaline-induced relaxations of histamine pre-contracted trachea after selective M 3 receptor alkylation. Our results suggest (i) that there is no evidence of M 2 receptor-mediated re-contraction of tracheal smooth muscle after M 3 receptor alkylation and stimulation of adenylyl cyclase, but (ii) that activation of M 2 receptors, after M 3 receptor alkylation, has a small inhibitory effect on relaxant responses to isoprenaline in guinea-pig tracheal smooth muscle. Therefore, it appears that the major role of postjunctional muscarinic M 2 receptors in guinea-pig trachea remains to be determined.