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

FEBS Letters

Hillard, Cecilia J¹  Kearn, Christopher S¹  Muthian, Shanmugam¹ 

[1] Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226 USA

关键词: Calcium channel;    Inverse agonist;    SR141716A;    Win 55212-2;   

DOI  :  10.1016/S0014-5793(99)01253-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Cerebellar granule cells (CGCs) express the CB₁ subtype of cannabinoid receptor. CB₁ 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 CB₁ 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 CB₁ receptor in CGCs results in a decreased influx of calcium in response to membrane depolarization, resulting in a decreased activation of neuronal NOS.

【 授权许可】

Unknown