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,metabolism
Time Factors
Chemicals
Anti-Inflammatory Agents
Glucocorticoids
Phosphatidylcholines
Phospholipases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Blackwell G J
Flower R J
Nijkamp F P
Vane J R
References (27)
27 references, click to expand
-
The distribution and metabolism of arachidonic acid in rabbit platelets during aggregation and its modification by drugs.
Br J Pharmacol. 1977 Feb;59(2):353-66
PMID: 837023
-
The release of biologically active substances from isolated lungs by 5-hydroxytryptamine and tryptamine.
Br J Pharmacol. 1970 Nov;40(3):582P-583P
PMID: 5497834
-
Structure of porcine pancreatic prephospholipase A2.
Nature. 1976 Nov 25;264(5584):373-7
PMID: 1034213
-
Partial purification of rabbit aorta contracting substance-releasing factor and inhibition of its activity by anti-inflammatory steroids.
Nature. 1976 Oct 7;263(5577):479-82
PMID: 972692
-
Anti-inflammatory effects of estradiol on human blood leukocytes.
J Lab Clin Med. 1972 Sep;80(3):373-84
PMID: 4262411
-
Release of prostaglandins, a prostaglandin metabolite, slow-reacting substance and histamine from anaphylactic lungs, and its modification by catecholamines.
Naunyn Schmiedebergs Arch Pharmacol. 1974;284(3):279-93
PMID: 4139670
-
Control by TSH of a phospholipase A 2 activity, a limiting factor in the biosynthesis of prostaglandins in the thyroid.
FEBS Lett. 1973 Mar 15;30(3):253-60
PMID: 4349546
-
Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.
Nat New Biol. 1971 Jun 23;231(25):232-5
PMID: 5284360
-
Effects of anti-inflammatory drugs on prostaglandin biosynthesis.
Nat New Biol. 1972 Jul 26;238(82):104-6
PMID: 4505422
-
Release of rabbit aorta contracting substance (RCS) and prostaglandins induced by chemical or mechanical stimulation of guinea-pig lungs.
Br J Pharmacol. 1973 Oct;49(2):226-42
PMID: 4135341
-
The release of prostaglandins from lung and other tissues.
Ann N Y Acad Sci. 1971 Apr 30;180:363-85
PMID: 4106477
-
Selective inhibition by mepacrine of the release of "rabbit aorta contracting substance" evoked by the administration of bradykinin.
J Pharm Pharmacol. 1972 Feb;24(2):159-61
PMID: 4401974
-
Release of additional factors in anaphylaxis and its antagonism by anti-inflammatory drugs.
Nature. 1969 Jul 5;223(5201):29-35
PMID: 4389381
-
Biosynthesis of prostaglandins.
Fed Proc. 1972 Sep-Oct;31(5):1442-50
PMID: 4560273
-
Prostaglandin endoperoxides. VII. Novel transformations of arachidonic acid in guinea pig lung.
Biochem Biophys Res Commun. 1974 Dec 11;61(3):942-9
PMID: 4451568
-
Inhibition of release of prostaglandins as an explanation of some of the actions of anti-inflammatory corticosteroids.
Nature. 1975 Mar 27;254(5498):308-11
PMID: 163980
-
Release of spasmogenic substances induced by vasoactive amines from isolated lungs.
Br J Pharmacol. 1972 Nov;46(3):543P-544P
PMID: 4656627
-
The importance of phospholipase-A2 in prostaglandin biosynthesis.
Biochem Pharmacol. 1976 Feb 1;25(3):285-91
PMID: 817726
-
Biogenesis of chemotactic molecules by the arachidonate lipoxygenase system of platelets.
Nature. 1975 Oct 23;257(5528):680-1
PMID: 810723
-
Significance of phospholipase A for prostaglandin formation.
Ann N Y Acad Sci. 1971 Apr 30;180:123-5
PMID: 5286094
-
Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids.
Proc Natl Acad Sci U S A. 1976 May;73(5):1730-4
PMID: 1064044
-
Effects of local anaesthetics on phospholipases.
Biochim Biophys Acta. 1976 Jul 20;441(1):93-102
PMID: 952985
-
Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides.
Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994-8
PMID: 1059088
-
Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig.
Prostaglandins. 1975 Aug;10(2):343-55
PMID: 1178912
-
Hydrocortisone inhibits prostaglandin production by mouse fibrosarcoma cells.
Nature. 1975 Dec 25;258(5537):739-41
PMID: 1207759
-
Corticosteroids inhibit prostaglandin production by rheumatiod synovia.
Nature. 1975 Dec 25;258(5537):737-9
PMID: 1207758
-
Trypsin-induced phospholipase activity in human platelets.
Biochem J. 1976 Nov 15;160(2):405-8
PMID: 827290