Inhibition and Superactivation of the Calcium-Stimulated Isoforms of Adenylyl Cyclase: Role of G sub( beta gamma ) Dimers

• Published in: Journal of molecular neuroscience Vol. 27; no. 2; pp. 195 - 204
• Main Authors: Stelner, D, Avidor-Reiss, T, Schallmach, E, Saya, D, Vogel, Z
• Format: Journal Article
• Language: English
• Published: 01.10.2005
• ISSN: 0895-8696

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 G sub(i/o)- coupled receptor activation inhibits the activity of several AC isozymes, including Ca super(2+)/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 G sub( beta gamma ) subunits (G sub( beta gamma ) 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 G sub( beta gamma ) is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.