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Updated: Jul 18, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
Cyclosporine attenuates the adenylyl cyclase superactivation induced by chronic cannabinoid treatment
Hamid R Banafshe1, Mahmoud Ghazi-Khansari, Shahram Ejtemaei Mehr
1Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
Abstract:
Chronic cannabinoid treatment results in the development of tolerance. Adenylyl cyclase superactivation, induced by chronic cannabinoid agonist administration, is regarded as one of the molecular mechanisms leading to tolerance. In the present study, the effect of cyclosporine on adenylyl cyclase superactivation after chronic exposure to WIN 55,212-2, a cannabinoid receptor agonist, was studied. Chronic treatment (18 h) with WIN 55,212-2 induced a significant increase in cAMP levels in human astrocytoma cells (adenylyl cyclase superactivation). Acute treatment with cyclosporine (10 min) did not have any effect on WIN 55,212-2-induced adenylyl cyclase superactivation. But, chronic cyclosporine treatment (18 h), with concentration from 1 nM to 1 microM, attenuates the development of adenylyl cyclase superactivation after chronic WIN 55,212-2 treatment. Our findings show that cyclosporine attenuates chronic cannabinoid-mediated adenylyl cyclase superactivation.
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