BIOCHEMICAL AND PHARMACOLOGICAL CHARACTERIZATION OF CANNABINOID BINDING-SITES USING [H-3] SR141716A

THIS study describes the binding characteristics of cannabinoid bindin g sites expressed in rat cerebellar membranes using the tritiated deri vative of SR141716A, the newly described cannabinoid receptor antagoni st. A single population of high-affinity binding sites (K-D=0.59+/-0.0 8 nM; B-max=3.86+/-0.42 pmol mg(-1) of protein) was demonstrated. Kine tic, competition and saturation experiments give similar results in te rms of SR141716A affinity. Delta(9)-tetrahydrocannabinol and the 11-hy droxy derivative competitively inhibited the specific binding of [H-3] SR141716A (K-i=47+/-9 and 32+/-4 nM, respectively). The cannabinoid ag onist WIN55212-2 has a 25-fold lower affinity for [H-3]SR141716A than for [H-3]WIN55212-2, showing that the two ligands do not recognize the cannabinoid binding site in the same fashion.