Mediation by G protein βγ subunits of the opioid stimulation of adenylyl cyclase activity in rat olfactory bulb

Abstract

In the rat olfactory bulb, activation of opioid receptors enhances basal adenylyl cyclase (EC 4.6.1.1) activity and potentiates enzyme stimulation by G s-coupled neurotransmitter receptors in a pertussis toxin-sensitive manner. In the present study, we investigated the involvement of G protein βγ subunits by examining the effects of βγ scavengers and exogenously added βγ subunits of transducin (βγ t). The QEHA fragment of type II adenylyl cyclase (50 μM), a peptide that binds to and inactivates βγ, inhibited the maximal stimulation of adenylyl cyclase activity elicited by Leu-enkephalin (Leu-enk) by about 50%. Similarly, the GDP-bound form of the α subunit of transducin (5 nM–1.5 μM), another βγ scavenger, reduced both the opioid stimulation of basal adenylyl cyclase activity and the potentiation of vasoactive intestinal peptide-stimulated enzyme activity. Under the same experimental conditions, these agents failed to affect the stimulation of the enzyme activity elicited by activation of β-adrenergic receptors with 1-isoproterenol. Moreover, the addition of βγ t (400 nM) stimulated basal adenylyl cyclase by 80%, and this effect was not additive with that produced by Leu-enk. The data indicate that opioids enhance adenylyl cyclase activity in rat olfactory bulb by promoting the release of βγ subunits from pertussis toxin-sensitive G proteins G i/G o.