Differential receptor-G-protein coupling evoked by dissimilar cannabinoid receptor agonists

被引:48
作者
Houston, DB [1 ]
Howlett, AC [1 ]
机构
[1] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA
关键词
aminoalkylindole drugs; cannabinoid drugs; cation-binding sites; desacetyllevonantradol; G-protein-coupled receptors; SR141716A; WIN55212-2;
D O I
10.1016/S0898-6568(98)00013-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Multiple affinity states are revealed by agonist competition for radioantagonist [H-3]SR141716A binding to rat brain CB1 cannabinoid receptors. Desacetyllevonantradol (DALN), a tricyclic cannabinoid, and WIN55212-2, an aminoalkylindole, both bound in two discrete affinity scares (30% high affinity), but the ratios of the IC50 revealed distinct differences. Other affinity-state differences between the agonists were: Na+ reduced the affinity for the membrane-bound receptor by 10-fold for DALN but minimally for WIN55212-2; a nonhydrolysable GTP analogue decreased the fraction of high-affinity WIN55212-2 binding but not that of DALN unless Na+ was also present. Detergent solubilisation increased the fraction of high-affinity binding for both agonists but eliminated any effect of Naf on the agonist affinities. In detergent solution, the GTP analogue reduced the WIN55212-2 high-affinity fraction but not that of DALN, even though the IC50 values increased for both DALN and WIN55212-2. The differential modulation of CBI receptor-G-protein coupling by Nai and guanine nucleotides is dependent upon the cannabimimetic agonist bound. (C) 1998 Elsevier Science Inc.
引用
收藏
页码:667 / 674
页数:8
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