ROLE OF G-PROTEIN BETA-GAMMA-SUBUNITS IN MUSCARINIC RECEPTOR-INDUCED STIMULATION AND INHIBITION OF ADENYLYL-CYCLASE ACTIVITY IN RAT OLFACTORY-BULB

In the olfactory bulb, muscarinic receptors exert a bimodal control on cyclic AMP, enhancing basal and G(s)-stimulated adenylyl cyclase acti vities and inhibiting the Ca2+/calmodulin- and forskolin-stimulated en zyme activities. In the present study, we investigated the involvement of G protein beta gamma subunits by examining whether the muscarinic responses were reproduced by the addition of beta gamma subunits of tr ansducin (beta gamma(t)) and blocked by putative beta gamma scavengers . Membrane incubation with beta gamma(t) caused a stimulation of basal adenylyl cyclase activity that was not additive with that produced by carbachol. Like carbachol, beta gamma(t) potentiated the enzyme stimu lations elicited by vasoactive intestinal peptide and corticotropin-re leasing hormone. RT-PCR analysis revealed the expression of mRNAs enco ding both type II and type IV adenylyl cyclase, two isoforms stimulate d by py synergistically with activated G(s). In addition, beta gamma(t ) inhibited the Ca2+/calmodulin- and forskolin-stimulated enzyme activ ities, and this effect was not additive with that elicited by carbacho l, Membrane incubation with either one of two beta gamma scavengers, t he GDP-bound form of the alpha subunit of transducin and the QEHA frag ment of type II adenylyl cyclase, reduced both the stimulatory and inh ibitory effects of carbachol. These data provide evidence that in rat olfactory bulb the dual regulation of cyclic AMP by muscarinic recepto rs is mediated by beta gamma subunits likely acting on distinct isofor ms of adenylyl cyclase.