Mediation by G protein betagamma subunits of the opioid stimulation of adenylyl cyclase activity in rat olfactory bulb.
In the rat olfactory bulb, activation of opioid receptors enhances basal adenylyl cyclase (EC 4.6.1.1) activity and potentiates enzyme stimulation by Gs-coupled neurotransmitter receptors in a pertussis toxin-sensitive manner. In the present study, we investigated the involvement of G protein betagamma subunits by examining the effects of betagamma scavengers and exogenously added betagamma subunits of transducin (betagamma(t)). The QEHA fragment of type II adenylyl cyclase (50 microM), a peptide that binds to and inactivates betagamma, inhibited the maximal stimulation of adenylyl cyclase activity elicited by Leu-enkephalin (Leu-enk) by about 50%. Similarly, the GDP-bound form of the alpha subunit of transducin (5 nM-1.5 microM), another betagamma 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 beta-adrenergic receptors with 1-isoproterenol. Moreover, the addition of betagamma(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 betagamma subunits from pertussis toxin-sensitive G proteins Gi/Go.
Department of Neuroscience, University of Cagliari, Italy. onali@unica.it
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D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000187:drug effects* / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015293:Transducin / Q000737:chemistry / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D009294:Narcotics; D010446:Peptide Fragments; D019204:GTP-Binding Proteins; D015293:Transducin; D000262:Adenylyl Cyclases