Nickl, Kathrin and Gardner, Eric E. and Geiger, Sarah and Heilmann, Joerg and Seifert, Roland (2008) Differential coupling of the human cannabinoid receptors hCB(1)R and hCB(2)R to the G-protein G alpha(i2)beta(1)gamma(2). NEUROSCIENCE LETTERS, 447 (1). pp. 68-72. ISSN 0304-3940, 1872-7972
Full text not available from this repository. (Request a copy)Abstract
Human cannabinoid receptors 1 (hCB(1)R) and 2 (hCB(2)R) are expressed in the CNS and couple to G(i)/G(o)-proteins. The aim of this study was to compare coupling of hCB(1)R and hCB(2)R to G alpha(i2)beta(1)gamma(2) in Sf9 insect cells. High-affinity agonist binding at hCB(1)R, but not at hCB(2)R, was resistant to guanine nucleotides. hCB(1)R activated G alpha(i2)beta(1)gamma(2) much more rapidly than hCB(2)R in the [S-35]guanosine 5'-[y-thioItriphosphate ([S-35]GTP-YS) binding assay. Moreover, hCB(1)R exhibited a higher constitutive activity than hCB(2)R as assessed by the relative inhibitory effects of inverse agonists on [S-35]GTP-yS binding and steady-state high-affinity GTPase activity compared to the stimulatory effects of the hCB(1/2)R agonist CP 55,940 [(-)-cis-3-[2-hydroxy-4-(1,1dimethylheptyl)phenyll-trans-4-(3-hydroxypropyl)cyclohexanol]. G alpha(i2)beta(1)gamma(2) coupled to hCB(2)R exhibited higher GDP- and GTP gamma S-affinities than G alpha(i2)beta(1)gamma(2) coupled to hCB(1)R. NaCl effectively reduced constitutive activity of hCB(1)R but not of hCB(2)R. Collectively, hCB(1)R and hCB(2)R couple differentially to G alpha(i2)beta(1)gamma(2). Moreover, hCB(1)R exhibits higher constitutive activity than hCB(2)R. These differences point to distinct functions of hCB(1)R and hCB(2)R in the CNS. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MASS SPECTROSCOPIC ANALYSIS; INVERSE AGONIST; CB2 RECEPTORS; CONSTITUTIVE ACTIVITY; BACULOVIRUS SYSTEM; PURIFICATION; Cannabinoid receptors; Constitutive activity; G(i)-proteins; GTP gamma S binding; GTPase; Sf9 insect cells |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Oct 2020 09:37 |
| Last Modified: | 14 Oct 2020 09:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29938 |
Actions (login required)
 |
View Item |
