Phospholipase A2 activity of guinea-pig isolated perfused lungs: stimulation, and inhibition by anti-inflammatory steroids

Br J Pharmacol. 1978 Jan;62(1):79-89. doi: 10.1111/j.1476-5381.1978.tb07009.x.

Abstract

1 A simple double-isotope assay for phospholipase A2 activity of perfused organs is described; Guinea-pig lungs perfused through the pulmonary circulation exhibit a low background enzyme activity. This activity is blocked by dexamethasone, betamethasone and hydrocortisone, mepacrine, procaine or chlorpromazine. Aspirin and indomethacin are without effect. 3 Mechanical trauma, antigen challenge or injections of bradykinin, rabbit aorta contracting substance-releasing factor (RCS-RF) or histamine increase "basal" phospholipase activity. The effect of these agents, except that of bradykinin, is blocked by dexamethasone or mepacrine. 4 The blocking effect of steroids is cumulative and dose-dependent. They do not work in cell-free systems. Inhibition by mepacrine is rapid and is effective in cell-free lung homogenates. 5 It is suggested that agents which liberate prostaglandin endoperoxides and thromboxane A2 from perfused lungs do so by activating phospholipase A2.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Glucocorticoids / pharmacology*
  • Guinea Pigs
  • Hydrolysis
  • In Vitro Techniques
  • Lung / enzymology*
  • Male
  • Perfusion
  • Phosphatidylcholines / pharmacology
  • Phospholipases / antagonists & inhibitors
  • Phospholipases / metabolism*
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Phosphatidylcholines
  • Phospholipases