‘Antiflammins’: Two nonapeptide fragments of uteroglobin and lipocortin I have no phospholipase A2 ‐inhibitory and anti‐inflammatory activity

FEBS Letters

Rink, H.¹  Marki, F.¹  Wiesenberg, I.¹  Pfeilschifter, J.¹ 

[1] Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd, CH-4002 Basel, Switzerland

关键词: Lipocortin;    Uteroglobin;    Nonapeptide;    Phospholipase A2;    Eicosanoid;    Inflammation;    DICD;    diisopropylcarbodiimide;    DMA;    dimethyl-acetamide;    FAB-MS;    fast atom bombardment mass spectrometry;    Fmoc;    fluorenyl-methoxy-carbonyl;    HOBt;    1-hydroxy-benzotriazole;    LTC4;    leukotriene C4;    MEM;    modified Eagle's medium;    PGE2;    prostaglandin E2;    PLA2;    phospholipase A2;    TFA;    trifluoroacetic acid;   

DOI  :  10.1016/0014-5793(90)80241-A

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The ‘antiflammin’ nonapeptides P1 and P2 [(1988) Nature 335, 726-730] were synthesized and tested for inhibition of phospholipase A₂ and release of prostaglandin E₂, and leukotriene C₄ in stimulated cells in vitro, and in vivo for anti-inflammatory activity in rats with carrageenan-induced paw oedema. Porcine pancreatic phospholipase A₂, was not inhibited at concentrations of 0.5–50 μM. Prostaglandin E₂, and leukotriene C₄ release by mouse macrophages stimulated with zymosan or ATP was not affected up to a concentration of 10 μm, nor was prostaglandin release by interleukin 1β-stimulated mesangial cells and angiotensin II-stimulated smooth muscle cells. Both peptides exhibited no anti-inflammatory activity in carrageenan-induced rat paw oedema after topical (250 μg/paw) or systemic administration (1 or 4 s.c.). These results do not support the claim of potent phospholipase A₂-inhibitory and anti-imflammatory activity of the ‘antiflammins’ P1 and P2 [1].

【 授权许可】

Unknown