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

Biochem Pharmacol. 1999 Mar 15;57(6):649-52. doi: 10.1016/s0006-2952(98)00326-8.

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 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.

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Enzyme Activation / drug effects
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / metabolism*
  • In Vitro Techniques
  • Male
  • Narcotics / pharmacology*
  • Olfactory Bulb / drug effects*
  • Olfactory Bulb / enzymology
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Transducin / chemistry
  • Transducin / pharmacology

Substances

  • Adenylyl Cyclase Inhibitors
  • Narcotics
  • Peptide Fragments
  • GTP-Binding Proteins
  • Transducin
  • Adenylyl Cyclases