Role of cannabinoid CB1 receptors and Gi/o protein activation in the modulation of synaptosomal Na+,K+-ATPase activity by WIN55,212-2 and ▵9-THC

摘要: In the present study, we evaluated effects of synthetic cannabinoid receptor agonist (R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN55,212-2) and active component Cannabis delta-9-tetrahydrocannabinol (triangle up(9)-THC) on Na(+),K(+)-ATPase activity in synaptosomal mice brain preparation. Additionally, potential exogenous cannabinoids endogenous opioid peptides interaction as well role G(i/o) proteins mediating activation were also explored. The ouabain-sensitive was measured whole-brain pure intact synaptosomes (obtained by Percoll gradient method) female CF-1 calculated difference between total ouabain (1 mM)-insensitive activities. Incubation vitro with WIN55,212-2 (0.1 pM-10 microM) or triangle up(9)-THC pM-0.1 microM), a concentration-dependent manner, stimulated activity. less potent but more efficacious than up(9)-THC. N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM-251) (10 nM), CB(1) selective antagonist, had not effect per se antagonized enhancement induced both, AM-251 produced significant reduction E(max) cannabinoid-induced increase activity, did significantly modify their EC(50). On other hand, co-incubation naloxone an completely failed to Na(+),K(+)-ATPase. Finally, pre-incubation 0.5 microg pertussis toxin (G(i/o) protein blocker) abolished WIN55,212-2. A lower dose, 0.25 microg, decreased 70% affect its These results suggest that WIN55212-2 indirectly enhance activating receptors naloxone-insensitive manner. addition, neuronal is apparently due proteins.