Desensitization of endogenously expressed delta-opioid receptors: no evidence for involvement of G protein-coupled receptor kinase 2

作者：Willets J; Kelly E^*

来源：European Journal of Pharmacology, 2001, 431(2): 133-141.

DOI：10.1016/S0014-2999(01)01360-7

• desensitization
• G protein-coupled receptor kinase
• delta-opioid receptor
• NG108-15 cell

The involvement of G protein-coupled receptor kinase 2 (GRK2) in the agonist-induced desensitization of delta -opioid receptor-mediated inhibition of cAMP formation in NG108-15 mouse neuroblastoma x rat glioma hybrid cells was investigated. Pretreatment of wild-type cells with the delta -opioid receptor agonist [D-Pen(2.5)]-enkephalin (DPDPE; 100 nM) for as little as 5 min produced marked desensitization of subsequent DPDPE-mediated inhibition of iloprost (300 nM)-stimulated cAMP formation. In NG108-15 cells stably overexpressing wild-type GRK2 or dominant negative mutant GRK2 (DNM GRK2), the DPDPE-induced desensitization of cAMP inhibition was the same as in plasmid-transfected control cells. Pretreatment of wild-type cells with the inhibitors of receptor internalization, concanavalin A (0.25 mg ml(-1)) or hypertonic sucrose (0.4 M), also failed. to inhibit DPDPE-mediated desensitization. Finally, in NG108-15 cells stably overexpressing G protein-coupled receptor kinase 6 (GRK6), DPDPE-induced desensitization was significantly increased as compared to plasmid-transfected control cells. These results indicate that GRK2 is unlikely to mediate the desensitization of endogenous delta -opioid receptors in NG108-15 cells, but that other GRKs, such as GRK6, may be more important.

• 出版日期2001-11-16