guanosine-triphosphate has been researched along with 2-4-diaminohypoxanthine* in 2 studies
2 other study(ies) available for guanosine-triphosphate and 2-4-diaminohypoxanthine
| Article | Year |
|---|---|
Tetrahydrobiopterin is a limiting factor of nitric oxide generation in interleukin 1 beta-stimulated rat glomerular mesangial cells.
Treatment of mesangial cells with recombinant human interleukin 1 beta (IL-1 beta) triggers the expression of a macrophage-type of nitric oxide (NO) synthase and the subsequent increase of cellular concentration of cGMP and nitrite production. Tetrahydrobiopterin (BH4) is an essential cofactor for NO synthase, and in the present study we investigated its impact on inducible NO synthesis in mesangial cells. Inhibition of GTP-cyclohydrolase I, the rate-limiting enzyme for BH4 synthesis, with 2,4-diamino-6-hydroxy-pyrimidine (DAHP) potently suppresses IL-1 beta-induced nitrite production and elevation of cellular cGMP levels. This inhibitory effect of DAHP is reversed by sepiapterin, which provides BH4 via the pterin salvage pathway. Most importantly, sepiapterin dose-dependently augments IL-1 beta-stimulated NO synthesis, indicating that the availability of BH4 limits the production of NO in cytokine-induced mesangial cells. N-acetylserotonin, an inhibitor of the BH4 synthetic enzyme sepiapterin reductase, completely abolishes IL-1 beta-stimulated nitrite production, whereas methotrexate, which inhibits the pterin salvage pathway, displays only a moderate inhibitory effect, thus suggesting that mesangial cells predominantly synthesize BH4 by de novo synthesis from GTP. In conclusion, these data demonstrate that BH4 synthesis is an absolute requirement for, and limits IL-1 beta induction of NO synthesis in mesangial cells. Inhibition of BH4 synthesis may provide new therapeutic approaches to the treatment of pathological conditions involving increased NO formation. Topics: Amino Acid Oxidoreductases; Animals; Biopterins; Cells, Cultured; Dose-Response Relationship, Drug; Glomerular Mesangium; GTP Cyclohydrolase; Guanosine Triphosphate; Hypoxanthines; Interleukin-1; Nitric Oxide; Nitric Oxide Synthase; Pteridines; Pterins; Rats; Recombinant Proteins | 1994 |
Biopterin. VII. Inhibition of synthesis of reduced biopterins and its bearing on the function of cerebral tryptophan-5-hydroxylase in vivo.
Repeated intraventricular injections of 2,4-diamino-6-hydroxypyrimidine (DAO-Pyr), inhibitor of D-erythro-q-dihydroneopterin triphosphate synthetase, inhibited q-BH2 synthesis from GTP, markedly increased accumulation of 2-amino-4-hydroxy-5 (or -6)-formamido-6-triphosphoribosylaminopyrimidine (FPyd-P3) and brought about a 60% decrease in the in vivo of reduced biopterin (BH2 and BH4) pool in the brain. Nevertheless, there was no effect on the rate of hydroxylation of L-tryptophan or on the 5-hydroxytryptamine level in rat brain. These data emphasized the significance of the rate of hydrogen transfer and the limitation of the concept of "unsaturation" (i.e., the absolute amount of the carrier pterin molecule) for the synthesis of neurotransmitters in vivo. Topics: Animals; Biopterins; Brain; Guanosine Triphosphate; Hypoxanthines; Pteridines; Pyrimidine Nucleotides; Rats; Serotonin; Tryptophan Hydroxylase | 1981 |