Effects of CB1 cannabinoid receptor activation on cerebellar granule cell nitric oxide synthase activity

Cerebellar granule cells (CGCs) express the CBI subtype of cannabinoid rece ptor, CB1 receptor agonists Win 55212-2, CP55940 and HU210 inhibit KCl-indu ced activation of nitric oxide synthase (NOS) in CGCs, Win 55212-2 has no e ffect on either basal NOS activity or on activation by N-methyl-D-aspartate and its effect is abolished by pre-treatment of the cells with pertussis t oxin. The CB1 receptor antagonist/inverse agonist SR141716A both reverses t he effects of Win 55212-2 and produces an increase in NOS activity that is additive with KCI, These results support the hypothesis that activation of the CB1 receptor in CGCs results in a decreased influx of calcium in respon se to membrane depolarization, resulting in a decreased activation of neuro nal NOS. (C) 1999 Federation of European Biochemical Societies.