Watson_1995_Eur.J.Pharmacol_294_779

Smooth muscles of a number of species contain both muscarinic M2 and M3 receptors in differing proportions and while muscarinic M3 receptors mediate contraction, the role of muscarinic M2 receptors is unclear. Muscarinic M2 receptor-mediated inhibition of adenylyl cyclase activity has been demonstrated in smooth muscle and since beta-adrenoceptor relaxation of this tissue is mediated via stimulation of adenylyl cyclase, an interaction between muscarinic M2 receptors and beta-adrenoceptors in smooth muscle has been postulated. Such an interaction has been demonstrated in guinea-pig ileum and trachea using two different approaches. The present study investigates whether interactions between muscarinic M2 receptors and beta-adrenoceptors also occur in guinea-pig oesophageal muscularis mucosae. Using the technique of selective muscarinic M3 receptor alkylation, we were unable to demonstrate muscarinic M2 receptor-mediated re-contractions in oesophageal smooth muscle, as described previously in ileum. In addition, while increased functional antagonism of relaxant responses to isoprenaline could be demonstrated in tissues pre-contracted with oxotremorine M compared to histamine, muscarinic M2 receptor activation did not contribute to this effect, as described previously in trachea. These data suggest a lack of interaction between muscarinic M2 receptors and beta-adrenoceptors in guinea-pig oesophageal smooth muscle, but suggest an interaction between muscarinic M3 receptors and beta-adrenoceptors.