title: Selective prostaglandin G/H synthase (PGHS)-2 inhibitors show greater inhibitory activities on human PGHS-2 than on murine PGHS-2 in intact cells.
abstract: Excess eicosanoid formation during inflammation has been attributed to the expression of the gene coding for the inducible isoform of prostaglandin G/H synthase (PGHS-2). Human and murine PGHS-2 proteins differ in 73 out of the 604 amino acids. When comparing the inhibitory effects of a panel of PGHS-inhibitors in a whole cell human and murine PGHS-2 assay carried out under identical conditions, classical NSAIDs with the exception of aspirin and tenoxicam showed similar inhibitory effects on both human and murine PGHS-2 enzymes. However, the PGHS-2 selective inhibitors nimesulide, flosulide and NS398 showed a much greater inhibition of human PGHS-2. We suggest that these differences could be due to the genetic differences of human and murine PGHS-2.
authors: Department of Pharmacology, TopCro Pharma Research GmbH, Linz, Austria.
authors: J
authors: J
authors: Berg
authors: H
authors: H
authors: Fellier
authors: A
authors: A
authors: Bodenteich
authors: T
authors: T
authors: Christoph
authors: R
authors: R
authors: Towart
references: Prostaglandins. 1994 Jan;47(1):55-9
references: 8140262
references: Fundam Clin Pharmacol. 1996;10(1):1-17
references: 8900495
references: J Biol Chem. 1991 Jul 15;266(20):12866-72
references: 1712772
references: Arzneimittelforschung. 1995 Oct;45(10):1093-5
references: 8595066
references: Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7384-8
references: 1380156
references: J Biol Chem. 1993 Aug 25;268(24):18234-42
references: 8349699
references: Trends Pharmacol Sci. 1995 Dec;16(12):413-7
references: 8578614
references: J Clin Invest. 1992 Jan;89(1):97-108
references: 1729286
references: Inflamm Res. 1995 Jun;44(6):253-7
references: 7583521
references: Biochem Biophys Res Commun. 1993 Dec 15;197(2):494-500
references: 7916614
references: J Pharmacol Exp Ther. 1994 Sep;270(3):1340-4
references: 7932188
references: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3228-32
references: 8159730
references: J Pharm Pharmacol. 1993 Aug;45(8):753-5
references: 8229647
references: J Pharmacol Exp Ther. 1995 Sep;274(3):1531-7
references: 7562530
references: J Clin Invest. 1996 Jun 1;97(11):2672-9
references: 8647962
references: J Biol Chem. 1996 Jun 28;271(26):15810-4
references: 8663121
references: Nature. 1994 Jan 20;367(6460):243-9
references: 8121489
references: Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12013-7
references: 7991575
references: J Pharmacol Toxicol Methods. 1997 Jun;37(4):179-86
references: 9279772
references: Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7
references: 8265610
references: Biochim Biophys Acta. 1996 Jan 5;1299(1):125-40
references: 8555245
references: Inflamm Res. 1995 Jan;44(1):1-10
references: 7664022
references: Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2046-50
references: 7510883
references: Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11202-6
references: 7972034
references: J Biol Chem. 1993 Mar 25;268(9):6610-4
references: 8454631
references: Cancer Metastasis Rev. 1994 Dec;13(3-4):241-56
references: 7712587
references: Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4888-92
references: 1594589
references: Biochim Biophys Acta. 1991 Apr 24;1083(1):1-17
references: 1903304