MUSCARINIC M(2) RECEPTORS DO NOT PARTICIPATE IN THE FUNCTIONAL ANTAGONISM BETWEEN METHACHOLINE AND ISOPRENALINE IN GUINEA-PIG TRACHEAL SMOOTH-MUSCLE

We investigated whether muscarinic M(2) receptors, known to inhibit ad enylyl cyclase activity in airway smooth muscle, also inhibit isoprena line-induced relaxation of guinea pig tracheal smooth muscle, as has r ecently been described for the dog (Fernandes et al., 1992, J. Pharmac ol. Exp. Ther. 262, 119). Smooth muscle strips were contracted with va rious concentrations of methacholine or histamine (which served as a c ontrol) in the absence or presence of the M(2)-selective muscarinic re ceptor antagonist, gallamine (30 mu M), and cumulative isoprenaline-re laxation curves were obtained. It was found that muscarinic M(2) recep tor blockade had no significant effect on isoprenaline pD(2) and E(max ) values, neither with histamine nor with methacholine. The results sh ow that, in guinea pig trachea, muscarinic M(2) receptors do not signi ficantly influence the functional antagonism of cholinergic smooth mus cle contraction by isoprenaline.