Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins
Methods were developed for quantitative determination of the three major metabolites of arachidonic acid in human platelets, i.e., 12L-hydroxy-5,8,10,14-cicosatetraenoic acid (HETE), 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (PHD). Aggregation of washed platelets by thrombin was accompanied by release of 1163 to 2175 ng/ml of HETE, 1129 to 2430 ng/ml of HHT, and 998 to 2299 ng/ml of PHD. The amount of PGG/sub 2/ (prostaglandin G/sub 2/) produced as calculated from the sum of the amounts of its metabolites (HHT and PHD) was 2477 to 5480 ng/ml. In contrast, the amounts of PGF/sub 2/ (prostaglandin E/sub 2/) and PGF/sub 2..cap alpha../ (prostaglandin F/sub 2..cap alpha../) released were approximately two orders of magnitude lower. In this system, the prostaglandins thus exert their biological action through the endoperoxides, which are almost exclusively metabolized to nonprostanoate structures and only to a small extent to the classical prostaglandins. Platelets from subjects given aspirin produced less than 5% of the above mentioned amounts of HHT and PHD, whereas the production of HETE was stimulated about 3-fold. This provides additional evidence for our earlier proposal that the anti-aggregating effect of aspirin is through inhibition of PGG/sub 2/ formation.
- Research Organization:
- Karolinska Inst., Stockholm
- OSTI ID:
- 7086857
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 71:10; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ACETYLSALICYLIC ACID
ANALGESICS
ARACHIDONIC ACID
BIOCHEMISTRY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CARBOXYLIC ACIDS
CHEMICAL ANALYSIS
CHEMISTRY
DRUGS
HYDROXY ACIDS
METABOLITES
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PEROXIDES
PROSTAGLANDINS