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Titolo:
Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy agonist mediating CB1 receptor-dependent G-protein activation in rat cerebellar membranes
Autore:
Savinainen, JR; Jarvinen, T; Laine, K; Laitinen, JT;
Indirizzi:
Univ Kuopio, Dept Physiol, FIN-70211 Kuopio, Finland Univ Kuopio Kuopio Finland FIN-70211 Physiol, FIN-70211 Kuopio, Finland Univ Kuopio, Dept Pharmaceut Chem, FIN-70211 Kuopio, Finland Univ Kuopio Kuopio Finland FIN-70211 eut Chem, FIN-70211 Kuopio, Finland
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 3, volume: 134, anno: 2001,
pagine: 664 - 672
SICI:
0007-1188(200110)134:3<664:DSD2IA>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOSINE A(1) RECEPTOR; CANNABINOID RECEPTOR; BRAIN MEMBRANES; GUANOSINE-5'-O-(3-THIO)TRIPHOSPHATE BINDING; SIGNAL-TRANSDUCTION; ANANDAMIDE; LIGAND; AUTORADIOGRAPHY; 2-ARACHIDONYLGLYCEROL; STIMULATION;
Keywords:
cannabinoid; endocannabinoid; anandamide; 2-arachidonoylglycerol; cannabinoid receptor, [S-35]-GTP gamma S autoradiography; noladin ether;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Laitinen, JT Univ Kuopio, Dept Physiol, FIN-70211 Kuopio, Finland Univ Kuopio Kuopio Finland FIN-70211 -70211 Kuopio, Finland
Citazione:
J.R. Savinainen et al., "Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy agonist mediating CB1 receptor-dependent G-protein activation in rat cerebellar membranes", BR J PHARM, 134(3), 2001, pp. 664-672

Abstract

1 Two endocannabinoids, arachidonoyl ethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) bind and activate G-protein-coupled cannabinoid receptors, but limited data exist on their relative ability to activate G-proteins.2 Here we assess agonist potency and efficacy of various cannabinoids, including 2-AG, HU-310 (2-arachidonoyl glyceryl ether, a third putative endocannabinoid), HU-313 (another ether analogue of 2-AG), AEA, R-methanandamide (an enzymatically stable analogue of AEA), and CP-55,940 at rat brain CB1 receptors using agonist-stimulated [S-35]-GTP gammaS binding to cerebellar membranes and whole brain sections. Degradation of endocannabinoids under experimental conditions was monitored by HPLC.3 To enhance efficacy differences, agonist dose-response curves were generated using increasing GDP concentrations. At 10(-6) M GDP, all compounds, except HU-313, produced full agonists responses similar to2.5 fold over basal. The superior efficacy of 2-AG over all other compounds became evident byincreasing GDP (10(-5) and 10(-4) M).4 In membrane incubations, 2-AG was degraded by 85% whereas AEA and HU-310were stable. Pretreatment of membranes with phenylmethylsulphonyl fluorideinhibited 2-AG degradation, resulting in 2 fold increase in agonist potency. Such pretreatment had no effect on AEA potency.5 Responses in brain sections were otherwise consistent with membrane binding data, but 2-AG evoked only a weak signal in brain sections, apparently due to more extensive degradation.6 These data establish that even under conditions of substantial degradation, 2-AG is a full efficacy agonist, clearly more potent than AEA, in mediating CB1 receptor-dependent G-protein activity in native membranes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 00:24:52