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Inhibition of prostaglandin synthesis by indomethacin, a drug with anti-inflammatory properties, has been attributed to its action on fatty acid cyclooxygenase. However, prostaglandin synthesis would also be inhibited if precursor fatty acids were not supplied. We find that indomethacin inhibits phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) of rabbit polymorphonuclear leukocytes in dose-dependent fashion. Inhibition is immediate and readily detected at 1 micrometer. The extent of inhibition is the same over a 10-fold range of substrate concentration and over a 500-fold range of enzyme purification. Inhibition is of the noncompetitive type, with an apparent Ki of 12 micrometer. Four other phospholipases A2--from venoms of Russell viper, Crotalus adamanteus, and bee, and from pig pancreas--are unaffected by 50 micrometer indomethacin, which inhibits leukocyte phospholipase A2 by 70%. This inhibition at low concentrations may well be important in the effects of the drug on protaglandin synthesis and inflammatory responses.
L Kaplan, and
J Weiss, and
P Elsbach
May 1980,
Biochimica et biophysica acta,
L Kaplan, and
J Weiss, and
P Elsbach
January 1990,
Advances in experimental medicine and biology,
L Kaplan, and
J Weiss, and
P Elsbach
December 1997,
Cancer letters,
L Kaplan, and
J Weiss, and
P Elsbach
December 1981,
FEBS letters,
L Kaplan, and
J Weiss, and
P Elsbach
November 1996,
American journal of respiratory cell and molecular biology,
L Kaplan, and
J Weiss, and
P Elsbach
May 1988,
Nippon Ganka Gakkai zasshi,
L Kaplan, and
J Weiss, and
P Elsbach
January 1989,
Enzyme,
L Kaplan, and
J Weiss, and
P Elsbach
December 1963,
The American journal of physiology,
L Kaplan, and
J Weiss, and
P Elsbach
October 1983,
Pharmacological research communications,
L Kaplan, and
J Weiss, and
P Elsbach
March 1992,
Biochemical and biophysical research communications,
