Evidence of the existence of G(i)-coupled inhibitory modulation of adenylyl cyclase by muscarinic receptor in guinea-pig trachealis

The present study involved functional investigation of the signalling pathw ay of adenylyl cyclase inhibition by the muscarinic receptor. Methacholine pre-treatment of tracheal smooth muscle resulted in inhibition of isoprenal ine- and guanine nucleotide-stimulated adenylyl cyclase. The effect could b e reversed by pre-incubation of the tissue with the antibody that identifie s the C-terminal decapeptide of inhibitory G proteins 1 and 2 (G(i)1 and G( i)2) indiscriminately. Methacholine also abated the pertussis toxin-catalys ed ADP-ribosylation of G(i alpha). These results suggest the existence of M -2 and/or M-4 subtype of the muscarinic receptor in the tracheal smooth mus cle of guinea-pig.