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Titolo:
INHIBITION OF TETRAHYDROBIOPTERIN SYNTHESIS REDUCES IN-VIVO NITRIC-OXIDE PRODUCTION IN EXPERIMENTAL ENDOTOXIC-SHOCK
Autore:
BUNE AJ; BRAND MP; HEALES SJR; SHERGILL JK; CAMMACK R; COOK HT;
Indirizzi:
UNIV LONDON IMPERIAL COLL SCI & TECHNOL,SCH MED,DEPT HISTOPATHOL,NORFOLK PL LONDON W2 1PG ENGLAND UNIV LONDON IMPERIAL COLL SCI & TECHNOL,SCH MED,DEPT HISTOPATHOL LONDON W2 1PG ENGLAND UNIV LONDON,NEUROL INST,DEPT NEUROCHEM LONDON WC1N 3BG ENGLAND UNIV LONDON,UNIV LONDON KINGS COLL,DIV LIFE SCI,CTR STUDY MET BIOL & MED LONDON W8 7AH ENGLAND
Titolo Testata:
Biochemical and biophysical research communications
fascicolo: 1, volume: 220, anno: 1996,
pagine: 13 - 19
SICI:
0006-291X(1996)220:1<13:IOTSRI>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
VASCULAR SMOOTH-MUSCLE; L-ARGININE; MURINE MACROPHAGES; MESSENGER-RNA; SYNTHASE; NITRATE; GTP; LIPOPOLYSACCHARIDE; BIOSYNTHESIS; GENERATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
A.J. Bune et al., "INHIBITION OF TETRAHYDROBIOPTERIN SYNTHESIS REDUCES IN-VIVO NITRIC-OXIDE PRODUCTION IN EXPERIMENTAL ENDOTOXIC-SHOCK", Biochemical and biophysical research communications, 220(1), 1996, pp. 13-19

Abstract

Nitric oxide synthesis requires the cofactor tetrahydrobiopterin. We have examined the effect on nitric oxide synthesis in experimental endotoxic shock of 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, the first and rate limiting enzyme for tetrahydrobiopterin synthesis. Rats given lipopolysaccharide (LPS, 10 mg/kg) showed a large rise in plasma nitrate at 4 and 8 hours which was significantly reduced by DAHP (1 g/kg) given at the same time as LPS. Therewas a 40-50% reduction in the haem-NO signal detected in kidney by electron paramagnetic resonance spectroscopy. LPS produced hypotension at 3 hours and 6 hours and this was ameliorated at 6 hours in rats given DAHP. DAHP abolished the rise in kidney tetrahydrobiopterin levels seen 4 hours after LPS but no effect was seen on induction of induciblenitric oxide synthase (iNOS) as assessed by immunohistochemistry and reverse transcriptase PCR. consistent with the effect of DAHP being byreduction of tetrahydrobiopterin levels. The results show that inhibition of tetrahydrobiopterin synthesis is an effective strategy to reduce nitric oxide synthesis by iNOS in vivo. (C) 1996 Academic Press, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 15:53:12