Cyclic GMP elevation by 5-hydroxytryptamine is due to nitric oxide derived from endogenous nitrosothiol in NG108-15 cells.
To clarify the involvement of nitric oxide (NO) derived from nitrosothiols (RSNO) in 5-hydroxytryptamine (5-HT)-induced Ca(2+)-independent cGMP formation (CIGF) in NG108-15 cells, we investigated the effects of 5-HT on intracellular contents of RSNO as well as of NO metabolites. 5-HT stimulation resulted in an increase in the intracellular contents of nitrate and cGMP. RSNO was detected in NG108-15 cells and was decreased by 5-HT stimulation. Furthermore, the time course of nitrate increase was coincident with that of RSNO decrease. CarboxyPTIO inhibited 5-HT-induced CIGF, whereas oxyhemoglobin failed to inhibit it. The data suggest that NO is stored in a stable form as RSNO and that 5-HT stimulates NO generation from endogenous RSNO, which is followed by elevation of cGMP via activation of cytosolic guanylyl cyclase by NO in NG108-15 cells. We suggest the existence of a novel 5-HT signal transduction pathway involved in NO generation in NG108-15 cells.
Arima
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Ohshima
Y
Y
Mizuno
T
T
Kitamura
Y
Y
Segawa
T
T
Nomura
Y
Y
D000818:Animals; D006152:Cyclic GMP / Q000494:pharmacology*; D005910:Glioma; D006822:Hybrid Cells; D007700:Kinetics; D009447:Neuroblastoma; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000032:analysis; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D010108:Oxyhemoglobins; D013438:Sulfhydryl Compounds; D009599:Nitroprusside; D009569:Nitric Oxide; D012701:Serotonin; D006152:Cyclic GMP