(6R)-5,6,7,8-tetrahydro-L-biopterin modulates nitric oxide-associated soluble guanylate cyclase activity in the rat cerebellum.
(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.
Suntory Institute for Biomedical Research, Osaka, Japan.
Y
Y
Nunokawa
T
T
Ishihara
T
T
Kanai
T
T
Noguchi
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D002531:Cerebellum / Q000201:enzymology*; D003600:Cytosol / Q000201:enzymology; D006162:Guanylate Cyclase / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009249:NADP / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002147:Calmodulin; D009599:Nitroprusside; D001708:Biopterins; D009569:Nitric Oxide; D009249:NADP; D001120:Arginine; D006162:Guanylate Cyclase; C003402:sapropterin; D002118:Calcium