ROLE OF MUSCARINIC M(2) AND M(3) RECEPTORS IN GUINEA-PIG TRACHEA - EFFECTS OF RECEPTOR ALKYLATION

Muscarinic M(2) receptors account for more than half the muscarinic re ceptor population in smooth muscles of a number of species and yet it is the smaller M(3) receptor population that mediates contraction of m any of these tissues. The role of the majority of M(2) receptors in th e control of smooth muscle tone is unclear. In guinea-pig ileal smooth muscle, an indirect contractile role (re-contraction) for M(2) recept ors has been demonstrated in tissues subjected to M(3) receptor alkyla tion and stimulation of adenylyl cyclase. The present studies have emp loyed the technique of irreversible receptor alkylation in order to in vestigate the role of muscarinic M(2) and M(3) receptors in the contro l of guinea-pig tracheal smooth muscle tone. Experiments were performe d to determine (i) whether an indirect contractile role for M(2) recep tors can be demonstrated in tracheal smooth muscle as described for il eum, and (ii) whether stimulation of M(2) receptors can inhibit isopre naline-induced relaxations of histamine pre-contracted trachea after s elective M(3) receptor alkylation. Our results suggest (i) that there is no evidence of M(2) receptor-mediated re-contraction of tracheal sm ooth muscle after M(3) receptor alkylation and stimulation of adenylyl cyclase, but (ii) that activation of M(2) receptors, after M(3) recep tor alkylation, has a small inhibitory effect on relaxant responses to isoprenaline in guinea-pig tracheal smooth muscle. Therefore, it appe ars that the major role of postjunctional muscarinic M(2) receptors in guinea-pig trachea remains to be determined.