Table 3

Additivity of the effects of agonists for cannabinoid, μ-opioid, and A1 adenosine receptors in wild-type and CB1 −/− brain membranes

AGONISTCB1+/+CB1−/−
WADPNet fmol/mg% AdditivityNet fmol/mg% Additivity
+ 168  ± 753  ± 2
+ 106  ± 322  ± 1
+ 70  ± 574  ± 6
+ 180  ± 13159  ± 8
+ + 170  ± 662  ± 156  ± 575  ± 5
+ + 240  ± 3101  ± 3122  ± 497  ± 5
+ + 311  ± 1190  ± 2200  ± 794  ± 1
+ + 175  ± 799  ± 384  ± 289  ± 5
+ + 261  ± 1191  ± 1188  ± 7104  ± 2
+ + 235  ± 1694  ± 3217  ± 1193  ± 1
+ + + 231  ± 896  ± 1125  ± 397  ± 4
+ + + 315  ± 1090  ± 2210  ± 697  ± 1
  • Stimulation of [35S]GTPγS binding by maximally effective concentrations of cannabinoid, μ-opioid, and A1 adenosine agonists to whole-brain membranes from CB1 +/+ and CB1 −/− mice. WIN55212-2 (W), anandamide (A), and DAMGO (D) were each added at 10 μM and PIA (P) at 1 μM either alone or in combination to determine the level of additivity among the agonists. Values shown are net-agonist stimulated femtomoles of [35S]GTPγS bound per milligram of membrane protein and percentage of additivity determined as described under Materials and Methods. % Additivity values near 100% additivity indicates pairs of ligands that probably act at different targets, whereas values substantially less than 100% imply that the pair of ligands are acting via the same G protein-coupled receptor. Values are mean ± S.E. from experiments conducted in triplicate in whole-brain membranes from three animals of each genotype.