Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase: role of Gbetagamma dimers

J Mol Neurosci. 2005;27(2):195-203. doi: 10.1385/jmn:27:2:195.

Abstract

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute Gi/o- coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute Mu-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of Gbetagamma subunits (Gbetagamma scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that Gbetagamma is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism*
  • Analgesics, Opioid / metabolism
  • Animals
  • COS Cells
  • Calcium / metabolism*
  • Chlorocebus aethiops
  • Colforsin / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • GTP-Binding Protein beta Subunits / metabolism*
  • GTP-Binding Protein gamma Subunits / metabolism*
  • Ionomycin / metabolism
  • Ionophores / metabolism
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism*
  • Morphine / metabolism
  • Pertussis Toxin / metabolism
  • Phosphodiesterase Inhibitors / metabolism
  • Rats
  • Receptors, Opioid, mu / metabolism*

Substances

  • Adenylyl Cyclase Inhibitors
  • Analgesics, Opioid
  • GTP-Binding Protein beta Subunits
  • GTP-Binding Protein gamma Subunits
  • Ionophores
  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Receptors, Opioid, mu
  • Colforsin
  • Ionomycin
  • Morphine
  • Pertussis Toxin
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Adenylyl Cyclases
  • Calcium