'Antiflammins': two nonapeptide fragments of uteroglobin and lipocortin I have no phospholipase A2-inhibitory and anti-inflammatory activity.
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 microM. Prostaglandin E2 and leukotriene C4 release by mouse macrophages stimulated with zymosan or ATP was not affected up to a concentration of 10 microM, nor was prostaglandin release by interleukin 1 beta-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 micrograms/paw) or systemic administration (1 or 4 mg/kg s.c.). These results do not support the claim of potent phospholipase A2-inhibitory and anti-inflammatory activity of the 'antiflammins' P1 and P2.
Märki
F
F
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Pfeilschifter
J
J
Rink
H
H
Wiesenberg
I
I
D000595:Amino Acid Sequence; D000818:Animals; D017302:Annexins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology*; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D013189:SRS-A / Q000378:metabolism; D013552:Swine; D014598:Uteroglobin / Q000494:pharmacology*
D017302:Annexins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D009842:Oligopeptides; D010446:Peptide Fragments; D013189:SRS-A; C064645:antiflammin P1; C064647:antiflammin P2; D014598:Uteroglobin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone