Opioid and Cannabinoid Receptors Share a Common Pool of GTP-Binding Proteins in Cotransfected Cells, But Not in Cells Which Endogenously Coexpress the Receptors |
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Authors: | Ma'anit Shapira Zvi Vogel Yosef Sarne |
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Institution: | (1) Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel;(2) Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel;(3) The Mauerberger Chair in Neuropharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel |
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Abstract: | 1. Opioid (, , ) and cannabinoid (CB1, CB2) receptors are coupled mainly toGi/Go GTP-binding proteins. The goal of the present study was to determine whether different subtypes of opioid and cannabinoid receptors, when coexpressed in the same cell, share a common reservoir, or utilize different pools, of G proteins.2. The stimulation of 35S]GTPS binding by selective opioid and cannabinoid agonists was tested in transiently transfected COS-7 cells, as well as in neuroblastoma cell lines. In COS-7 cells, cotransfection of - and -opioid receptors led to stimulation of 35S]GTPS binding by either -selective (DAMGO) or -selective (DPDPE) agonists. The combined effect of the two agonists was similar to the effect of either DAMGO or DPDPE alone, suggesting the activation of a common G-protein reservoir by the two receptor subtypes.3. The same phenomenon was observed when COS-7 cells were cotransfected with CB1 cannabinoid receptors and either - or -opioid receptors.4. On the other hand, in N18TG2 neuroblastoma cells, which endogenously coexpress CB1 and -opioid receptors, as well as in SK-N-SH neuroblastoma cells, which coexpress - and -opioid receptors, the combined effects of the various agonists (the selective cannabinoid DALN and the selective opioids DPDPE and DAMGO) were additive, implying the activation of different pools of G proteins by each receptorsubtype.5. These results suggest a fundamental difference between native and artificially transfected cells regarding the compartmentalization of receptors and GTP-binding proteins. |
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Keywords: | opioid receptors cannabinoid receptors GTP-binding proteins cell transfection [35S]GTPS binding" target="_blank">gif" alt="gamma" align="MIDDLE" BORDER="0">S binding neuroblastoma |
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