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

Cell Signal. 1998 Oct;10(9):667-74. doi: 10.1016/s0898-6568(98)00013-8.


Multiple affinity states are revealed by agonist competition for radioantagonist [3H]SR141716A binding to rat brain CB1 cannabinoid receptors. Desacetyllevonantradol (DALN), a tricyclic cannabinoid, and WIN55212-2, an aminoalkylindole, both bound in two discrete affinity states (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 Na+ 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 CB1 receptor-G-protein coupling by Na+ and guanine nucleotides is dependent upon the cannabimimetic agonist bound.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzoxazines
  • Binding Sites
  • Binding, Competitive
  • Brain / metabolism
  • Cannabinoids / antagonists & inhibitors
  • Cannabinoids / metabolism*
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • In Vitro Techniques
  • Morpholines / metabolism
  • Naphthalenes / metabolism
  • Phenanthridines / metabolism
  • Piperidines / metabolism
  • Pyrazoles / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists*
  • Receptors, Drug / metabolism*
  • Rimonabant
  • Sodium / pharmacology


  • Benzoxazines
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • Phenanthridines
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • desacetylnantradol
  • Sodium
  • GTP-Binding Proteins
  • Rimonabant