Selective prostaglandin G/H synthase (PGHS)-2 inhibitors show greater inhibitory activities on human PGHS-2 than on murine PGHS-2 in intact cells

被引：1

作者：

Berg J. ^{[1
]}

Fellier H. ^{[1
]}

Bodenteich A. ^{[1
]}

Christoph T. ^{[1
]}

Towart R. ^{[1
]}

机构：

[1] Department of Pharmacology, TopCro Pharma Research GmbH, Linz

来源：

InflammoPharmacology | 1997年 / 5卷 / 2期

关键词：

Flosulide; Nimesulide; NS398; NSAID; PGHS-2; inhibition;

D O I：

10.1007/s10787-997-0020-y

中图分类号：

学科分类号：

摘要：

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.

引用

页码：119 / 126

页数：7

共 29 条

[1]

Smith WL, Marnett LJ, Prostaglandin endoperoxide synthase: structure and catalysis, Biochim Biophys Acta., 1083, pp. 1-17, (1990)

[2]

Hershman HR, Regulation of prostaglandin synthase-1 and prostaglandin synthase-2, Cancer Metastasis Reviews., 13, pp. 241-56, (1994)

[3]

Anderson G, Hauser S, McGarity K, Bremer M, Isakson P, Gregory S, Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis, J Clin Invest., 97, pp. 2672-9, (1996)

[4]

Masferrer JL, Reddy ST, Zweifel BS, In vivo glucocorticoids regulate cyclooxygenase-2 but not cyclooxygenase-1 in peritoneal macrophages, J Pharmacol ExpTher., 270, pp. 1340-4, (1994)

[5]

Sano H, Hla T, Maier JAM, In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis in rats with adjuvant and streptococcal cell wall arthritis, J Clin Invest., 89, pp. 97-108, (1992)

[6]

Scibert K, Zhang Y, Leahy K, Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain, Proc Natl Acad Sci USA., 91, pp. 12013-7, (1994)

[7]

Vane JR, Mitchell JA, Appleton I, Inducible isoforms of cyclooxygenase and nitric-oxide synthase on inflammation, Proc Natl Acad Sci USA., 91, pp. 2046-50, (1994)

[8]

Hershman HR, Prostaglandin synthase 2, Biochim Biophys Acta., 1299, pp. 125-40, (1996)

[9]

Vane JR, Botting RM, New insights into the mode of action of anti-inflammatory drugs, Inflamm Res., 44, pp. l-10, (1995)

[10]

Battistini B, Botting R, Bakhle YS, COX-1 and COX-2: towards the development of more selective NSAIDs, Drug News Perspectives., 7, pp. 501-12, (1994)

← 1 2 3 →