Home LiteratureArticle Details
PMID: 193113 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Application of imidazole as a selective inhibitor thromboxane synthetase in human platelets.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 74 ·No. 4 ·1977-04-00 ·Pages 1716-20

Needleman P, Raz A, Ferrendelli JA, Minkes M

Abstract

Human platelet suspensions release a rabbit-aorta-contracting substance (previously identified as thromboxane A2) during aggregation produced by arachidonic acid, prostaglandin endoperoxide, thrombin, and collagen. Incubation of platelets with imidazole did not interfere with the aggregation produced by these agonists but markedly reduced the generation of the rabbit-aorta-contracting substance. We find that imidazole inhibited the conversion of exogenous or endogenous prostaglandin endoperoxide into thromboxane A2-Imidazole selectively inhibits thromboxane synthetase in intact human platelets, because this agent blocks the conversion of [14C]arachidonate into [14C]thromboxane B2 but does not inhibit the conversion of [14C]arachidonate into [14C]prostaglandin E2. The inhibition of thromboxane synthetase by imidazole is not the result of an alteration in platelet 3':5'-cyclic AMP levels. These results illustrate the utility of imidazole as a pharmacological tool and demonstrate the two unique and dissociable properties of the endoperoxides themselves--their ability to aggregate platelets and their enzymatic conversion to the potent vasoconstrictor thromboxane.

MeSH Terms
Blood Platelets/drug effects,enzymology Cyclic AMP/blood Humans Imidazoles/pharmacology Kinetics Oxidoreductases/antagonists & inhibitors Platelet Aggregation/drug effects
Chemicals
Imidazoles Cyclic AMP Oxidoreductases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Needleman P
Raz A
Ferrendelli J A
Minkes M
References (27)
27 references, click to expand
  1. 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
  2. Letter: Isolation, structure, and biosynthesis of 6-ketoprostaglandin F1 alpha in the rat stomach.
    J Am Chem Soc. 1976 Apr 14;98(8):2348-9 PMID: 1254872
  3. Adenosine 3',5'-phosphate in biological materials. I. Purification and properties of cyclic 3',5'-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3',5'-phosphate in human urine.
    J Biol Chem. 1962 Apr;237:1244-50 PMID: 13875173
  4. Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0 acetylation by acetic anhydride in aqueous solution.
    J Cyclic Nucleotide Res. 1975;1(4):207-18 PMID: 177461
  5. Modulation of platelet cyclic nucleotide content by PGE1 and the prostaglandin endoperoxide PGG2.
    J Cyclic Nucleotide Res. 1976;2(2):79-87 PMID: 177467
  6. A novel prostaglandin is the major product of arachidonic acid metabolism in rabbit heart.
    Proc Natl Acad Sci U S A. 1977 Jan;74(1):101-5 PMID: 264662
  7. Adenyl cyclase activity in human platelets.
    Biochem Biophys Res Commun. 1969 Apr 29;35(2):265-72 PMID: 4306327
  8. Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides.
    J Biol Chem. 1972 Feb 25;247(4):1106-13 PMID: 4334491
  9. Release of additional factors in anaphylaxis and its antagonism by anti-inflammatory drugs.
    Nature. 1969 Jul 5;223(5201):29-35 PMID: 4389381
  10. Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis.
    Proc Natl Acad Sci U S A. 1973 Mar;70(3):899-903 PMID: 4514999
  11. Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation.
    Proc Natl Acad Sci U S A. 1974 Feb;71(2):345-9 PMID: 4521806
  12. The generation from arachidonic acid of rabbit aorta contracting substance (RCS) by a microsomal enzyme preparation which also generates prostaglandins.
    Br J Pharmacol. 1972 Nov;46(3):449-57 PMID: 4656606
  13. Isolation and properties of intermediates in prostaglandin biosynthesis.
    Biochim Biophys Acta. 1973 Dec 20;326(3):448-61 PMID: 4776443
  14. Prostaglandins, oxygen tension and smooth muscle tone.
    Br J Pharmacol. 1972 Jul;45(3):451-62 PMID: 5072227
  15. A novel prostaglandin derivative formed from arachidonic acid by rat stomach homogenates.
    Biochemistry. 1971 Sep 28;10(20):3657-64 PMID: 5096392
  16. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation.
    Nature. 1976 Oct 21;263(5579):663-5 PMID: 802670
  17. Pharmacologic closure of patent ductus arteriosus in the premature infant.
    N Engl J Med. 1976 Sep 2;295(10):526-9 PMID: 820994
  18. Coronary tone modulation: formation and actions of prostaglandins, endoperoxides, and thromboxanes.
    Science. 1977 Jan 28;195(4276):409-12 PMID: 831285
  19. Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides.
    Nature. 1976 Jun 17;261(5561):558-60 PMID: 934294
  20. Endogenous formation of the prostaglandin endoperoxide metabolite, thromboxane B2, by brain tissue.
    Biochem Biophys Res Commun. 1976 Jun 7;70(3):907-13 PMID: 938532
  21. Thromboxanes: selective biosynthesis and distinct biological properties.
    Science. 1976 Jul 9;193(4248):163-5 PMID: 945611
  22. Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis.
    N Engl J Med. 1976 Sep 2;295(10):530-3 PMID: 950959
  23. Release of novel prostaglandins and thromboxanes after immunological challenge of guinea pig lung.
    Nature. 1976 Aug 19;262(5570):699-702 PMID: 958441
  24. Prostaglandin endoperoxide and thromboxane generating systems and their selective inhibition.
    Prostaglandins. 1976 Sep;12(3):323-35 PMID: 968048
  25. Paradoxical endogenous synthesis of a coronary dilating substance from arachidonate.
    Prostaglandins. 1976 Sep;12(3):337-53 PMID: 968049
  26. N-0164 inhibits generation of thromboxane-A2-like activity from prostaglandin endoperoxides by human platelet microsomes.
    Prostaglandins. 1976 Sep;12(3):465-9 PMID: 968059
  27. Prostaglandin antagonism by sodium p-benzyl-4-[1-oxo-2-(4-chlorobenzyl)-3-phenylpropyl]pheenyl phosphonate (N-0164).
    Br J Pharmacol. 1976 Nov;58(3):333-9 PMID: 990588
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.74.4.1716
Published
1977-04-00
Pages
1716-20
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC430864
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.74.4.1716 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2