Differential superactivation of adenylyl cyclase isozymes after chronic activation of the CB(1) cannabinoid receptor

Many types of cells exhibit increased adenylyl cyclase (AC) activity after chronic agonist treatment of G(i/o)-coupled receptors. This phenomenon, defined as AC superactivation or sensitization, has mostly been studied for the opioid receptors and is implicated in opiate addiction. Here we show that...

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Bibliographic Details
Published in:Molecular pharmacology 2000-04, Vol.57 (4), p.746-752
Main Authors: Rhee, M H, Nevo, I, Avidor-Reiss, T, Levy, R, Vogel, Z
Format: Article
Language:English
Subjects:
Adenylyl Cyclases - metabolism
Animals
Cannabinoids - pharmacology
CHO Cells
COS Cells
Cricetinae
Enzyme Activation
Isoenzymes - metabolism
Receptors, Cannabinoid
Receptors, Drug - agonists
Receptors, Drug - metabolism
Transfection
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Summary:Many types of cells exhibit increased adenylyl cyclase (AC) activity after chronic agonist treatment of G(i/o)-coupled receptors. This phenomenon, defined as AC superactivation or sensitization, has mostly been studied for the opioid receptors and is implicated in opiate addiction. Here we show that this phenomenon is also observed on chronic activation of the CB(1) cannabinoid receptor. Moreover, using COS-7 cells cotransfected with CB(1) receptor and individual AC isozymes, we could show selective superactivation of AC types I, III, V, VI, and VIII. The level of superactivation was dependent on the concentration of agonist and time of agonist exposure and was not dependent on the AC stimulator used. No superactivation of AC types II, IV, or VII was observed in COS-7 cells cotransfected with CB(1). The superactivation of AC type V was abolished by pretreatment with pertussis toxin and by cotransfection with the carboxy terminus of beta-adrenergic receptor kinase, which serves as a scavenger of G(betagamma) dimers, implying a role for the G(i/o) proteins and especially G(betagamma) dimers in the cannabinoid-induced superactivation of AC.
ISSN:0026-895X