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Cyclic GMP Elevation by 5-Hydroxytryptamine Is Due to Nitric Oxide Derived from Endogenous Nitrosothiol in NG108-15 Cells

https://doi.org/10.1006/bbrc.1996.1531Get rights and content

Abstract

To clarify the involvement of nitric oxide (NO) derived from nitrosothiols (RSNO) in 5-hydroxytryptamine (5-HT)-induced Ca2+-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.

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Abbreviations used: cGMP, cyclic guanosine 3′,5′-monophosphate; 5-HT, 5-hydroxytryptamine; NO, nitric oxide; carboxyPTIO, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazolin-1-oxyl 3-oxide; RSNO, nitrosothiol; NOS, nitric oxide synthase; SNP, sodium nitroprusside.

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