CYCLIC-GMP GENERATION MEDIATED BY 5-HT-2 RECEPTORS VIA NITRIC OXIDE-DEPENDENT PATHWAY AND ITS EFFECT ON THE DESENSITIZATION OF 5-HT-2 RECEPTORS IN C6 GLIOMA-CELLS

Serotonin (5-HT)-2 receptor-mediated cGMP generation was investigated in comparison with calcium (Ca2+) mobilization in C6 glioma cells. 5-H T enhanced cGMP generation, and risperidone and ketanserin potently bl ocked the response. These results indicate that 5-HT-2 receptors are r esponsible for the cGMP generation. 5-HT-induced cGMP production was c ompletely abolished by BAPTA, an intracellular Ca2+ chelating agent, o r N-G-monomethyl-L-arginine (NMMA), a nitric oxide synthase (NOS) inhi bitor, suggesting that 5-HT-induced cGMP generation was through nitric oxide (NO)-dependent pathway. 5-HT (10 mu)-elicited Ca2+ mobilization and cGMP generation were reduced to 40 and 15% after pretreatment wit h 10 mu M 5-HT for 4 hours. NMMA did not modify 5-HT-induced desensiti zation of either Ca2+ mobilization or cGMP generation, suggesting that NO pathway is independent of the desensitization. The present study h as demonstrated the nature of 5-HT-2 receptor-mediated cGMP generation in C6 glioma cells.