Abstract
Cerebellar granule cells (CGCs) express the CB 1 subtype of cannabinoid receptor. CB 1 receptor agonists Win 55212-2, CP55940 and HU210 inhibit KCl-induced activation of nitric oxide synthase (NOS) in CGCs. Win 55212-2 has no effect 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 toxin. The CB 1 receptor antagonist/inverse agonist SR141716A both reverses the effects of Win 55212-2 and produces an increase in NOS activity that is additive with KCl. These results support the hypothesis that activation of the CB 1 receptor in CGCs results in a decreased influx of calcium in response to membrane depolarization, resulting in a decreased activation of neuronal NOS.
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