AGONIST | CB1+/+ | CB1−/− | |||||
---|---|---|---|---|---|---|---|
W | A | D | P | Net fmol/mg | % Additivity | Net fmol/mg | % Additivity |
+ | 168 ± 7 | 53 ± 2 | |||||
+ | 106 ± 3 | 22 ± 1 | |||||
+ | 70 ± 5 | 74 ± 6 | |||||
+ | 180 ± 13 | 159 ± 8 | |||||
+ | + | 170 ± 6 | 62 ± 1 | 56 ± 5 | 75 ± 5 | ||
+ | + | 240 ± 3 | 101 ± 3 | 122 ± 4 | 97 ± 5 | ||
+ | + | 311 ± 11 | 90 ± 2 | 200 ± 7 | 94 ± 1 | ||
+ | + | 175 ± 7 | 99 ± 3 | 84 ± 2 | 89 ± 5 | ||
+ | + | 261 ± 11 | 91 ± 1 | 188 ± 7 | 104 ± 2 | ||
+ | + | 235 ± 16 | 94 ± 3 | 217 ± 11 | 93 ± 1 | ||
+ | + | + | 231 ± 8 | 96 ± 1 | 125 ± 3 | 97 ± 4 | |
+ | + | + | 315 ± 10 | 90 ± 2 | 210 ± 6 | 97 ± 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.