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

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...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2005, Vol.27 (2), p.195-203
Main Authors: Steiner, Debora, Avidor-Reiss, Tomer, Schallmach, Ester, Saya, Daniella, Vogel, Zvi
Format: Article
Language:English
Subjects:
Adenylyl Cyclase Inhibitors
Adenylyl Cyclases - metabolism
Analgesics, Opioid - metabolism
Animals
Calcium - metabolism
Cercopithecus aethiops
Colforsin - metabolism
COS Cells
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
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Summary: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.
ISSN:0895-8696