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Titolo:
Effects of selective and unselective cyclooxygenase inhibitors on prostanoid release from various rat organs
Autore:
Tegeder, I; Neupert, W; Guhring, H; Geisslinger, G;
Indirizzi:
Univ Frankfurt, Ctr Pharmacol, D-60590 Frankfurt, Germany Univ Frankfurt Frankfurt Germany D-60590 col, D-60590 Frankfurt, Germany
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 292, anno: 2000,
pagine: 1161 - 1168
SICI:
0022-3565(200003)292:3<1161:EOSAUC>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ARACHIDONIC-ACID METABOLISM; INDUCIBLE CYCLOOXYGENASE; GENE DISRUPTION; MESSENGER-RNA; IN-VIVO; INFLAMMATION; EXPRESSION; STOMACH; NS-398;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Geisslinger, G Univ Frankfurt, Ctr Pharmacol, Theodor Stern Kai 7, D-60590Frankfurt, Germany Univ Frankfurt Theodor Stern Kai 7 Frankfurt Germany D-60590
Citazione:
I. Tegeder et al., "Effects of selective and unselective cyclooxygenase inhibitors on prostanoid release from various rat organs", J PHARM EXP, 292(3), 2000, pp. 1161-1168

Abstract

It has been assumed that cyclooxygenase-2 (COX-2) is solely responsible for inflammatory processes. Recently, this view has been challenged because COX-2-selective agents caused a delay of gastric ulcer healing and exacerbation of inflammation in rats. To further characterize organ-specific toxic effects of selective and nonselective COX inhibitors, we assessed the eicosanoid release from different rat organs ex vivo after oral administration ofthe COX-2-selective inhibitor NS-398 and the unselective COX inhibitors diclofenac, meloxicam, and ketorolac. Prostanoid and leukotriene release fromtissue fragments of the stomach, kidney, lung, and brain were determined after ex vivo incubation of tissue fragments in Tyrode's solution for 10 minat 37 degrees C. Ketorolac (0.1, 0.3, and 0.9 mg/kg) inhibited prostanoid release from all organs most potently and led to a significant increase of leukotriene release from the lung. Effects of diclofenac and meloxicam (1, 3, and 9 mg/kg each) were similar for all organs tested. At 9 mg/kg, 6keto-prostaglandin F (PGF)(1 alpha) release from gastric mucosa was reduced by 79.1 +/- 11.4 and 87.6 +/- 7.7% and PGE(2) release from rat kidney was inhibited by 60.4 +/- 6.8 and 78.6 +/- 16.6% by diclofenac and meloxicam, respectively. NS-398 did not reduce prostanoid release from the lung. Consistent with the reported constitutive expression of COX-2, prostanoid release fromkidney and brain was reduced by 20 to 30%. The release of 6keto-PGF(1 alpha) from gastric mucosa was reduced by 34.7 +/- 22.2% at 3 mg/kg and by 86.9+/- 12.7% at 9 mg/kg. At these doses, NS-398 has been previously shown to be COX-2 selective. Because PGF(1 alpha) is the stable breakdown product ofPGI(2), these results suggest that COX-2 contributes to PGI(2) synthesis in the rat stomach.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 21:22:24