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Role of G Protein βγ Subunits in Muscarinic Receptor‐Induced Stimulation and Inhibition of Adenylyl Cyclase Activity in Rat Olfactory Bulb
Author(s) -
Olianas Maria C.,
Ingianni Angela,
Onali Pierluigi
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70062620.x
Subject(s) - adenylyl cyclase , adcy10 , medicine , adcy9 , forskolin , endocrinology , g protein , muscarinic acetylcholine receptor , carbachol , gs alpha subunit , biology , chemistry , stimulation , receptor , biochemistry
In the olfactory bulb, muscarinic receptors exert a bimodal control on cyclic AMP, enhancing basal and G s ‐stimulated adenylyl cyclase activities and inhibiting the Ca 2+ /calmodulin‐ and forskolin‐stimulated enzyme activities. In the present study, we investigated the involvement of G protein βγ subunits by examining whether the muscarinic responses were reproduced by the addition of βγ subunits of transducin (βγ t ) and blocked by putative βγ scavengers. Membrane incubation with βγ t caused a stimulation of basal adenylyl cyclase activity that was not additive with that produced by carbachol. Like carbachol, βγ t potentiated the enzyme stimulations elicited by vasoactive intestinal peptide and corticotropin‐releasing hormone. RT‐PCR analysis revealed the expression of mRNAs encoding both type II and type IV adenylyl cyclase, two isoforms stimulated by βγ synergistically with activated G s . In addition, βγ t inhibited the Ca 2+ /calmodulin‐ and forskolin‐stimulated enzyme activities, and this effect was not additive with that elicited by carbachol. Membrane incubation with either one of two βγ scavengers, the GDP‐bound form of the α subunit of transducin and the QEHA fragment of type II adenylyl cyclase, reduced both the stimulatory and inhibitory effects of carbachol. These data provide evidence that in rat olfactory bulb the dual regulation of cyclic AMP by muscarinic receptors is mediated by βγ subunits likely acting on distinct isoforms of adenylyl cyclase.