Effect of tetrahydrobiopterin on nitric oxide synthase-containing cells in the rat hippocampus

• Published in: Neuroscience research Vol. 50; no. 2; pp. 161 - 167
• Main Authors: Koshimura, Kunio, Murakami, Yoshio, Tanaka, Junko, Yamamoto, Masahiro, Kato, Yuzuru
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.10.2004
• Subjects: 2,4-Diamono-6-hydroxypyrimidine; Animals; Enzyme Inhibitors - pharmacology; Extracellular Fluid - chemistry; Extracellular Fluid - drug effects; Extracellular Fluid - metabolism; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Immunohistochemistry; Male; Neurons - drug effects; Neurons - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitric oxide synthase; Nitric Oxide Synthase - metabolism; Pterins; Rat; Rats; Sugar Acids - pharmacology; Tetrahydrobiopterin; Nitric oxide synthase; 2,4-Diamono-6-hydroxypyrimidine; Rat; Tetrahydrobiopterin; Nitric oxide; Hippocampus
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2004.06.012

We have observed that tetrahydrobiopterin (BH 4), a cofactor of nitric oxide synthase (NOS), acts as a self-protection factor against nitric oxide (NO) toxicity in PC12 cells. To further investigate the self-protection action of BH 4 in vivo, the effect of deletion of endogenous BH 4 on NO-producing cells was examined in the rat hippocampus. Following the peripheral infusion of 50 mM 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, using a miniosmotic pump for 14 days, BH 4 content in the hippocampus decreased as compared with the control group administered with vehicle solution, which had no effect on brain BH 4 content. When the rats were administered with 50 mM DAHP and 10 mM BH 4, the DAHP-induced decrease in BH 4 content was prevented. The extracellular concentration of NO metabolites remained unchanged following DAHP administration, suggesting that DAHP-induced decrease in BH 4 content had no effect on NO production. The number of NOS-positive cells decreased following DAHP administration in the hippocampal regions, while the number of NOS-negative cells remained unchanged. The DAHP-induced decrease in the NOS-positive cell number was prevented by the administration of 10 mM BH 4 and DAHP. These results suggest that endogenous BH 4 may affect NOS-positive cell number in the rat hippocampus.