(6R)-5,6,7,8-tetrahydro-L-biopterin modulates nitric oxide-associated soluble guanylate cyclase activity in the rat cerebellum.

Abstract:

:(6R)-5,6,7,8-Tetrahydro-L-biopterin (R-THBP) is a cofactor not only for aromatic amino acid hydroxylases in mammalian tissues but also for nitric oxide synthase (NOS) induced by endotoxins or cytokines in some kinds of cells. Recently it has been reported that nitric oxide (NO) has biological activity in endothelium and in brain as well. NO activates soluble guanylate cyclase (sGC). Superoxide reacts with NO easily and shortens the half-life of NO actions. We found, in a study using rat cerebellar cytosol fraction, that R-THBP itself did not directly activate sGC, but activated sGC at concentrations ranging from 0.1 to 10 microM only under NO generating conditions of activated NOS and in the presence of sodium nitroprusside. In addition, R-THBP (1 microM) did not alter the NOS activity, which was determined by L-citrulline formation. These results suggest that R-THBP may regulate sGC activity associated with NO formation in the central nervous system.

journal_name

Arch Biochem Biophys

authors

Nunokawa Y,Ishihara T,Kanai T,Noguchi T

doi

10.1016/0003-9861(92)90472-9

subject

Has Abstract

pub_date

1992-11-01 00:00:00

pages

726-30

issue

2

eissn

0003-9861

issn

1096-0384

pii

0003-9861(92)90472-9

journal_volume

298

pub_type

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