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. 1976 May;83(2):283–298.

Localization of platelet prostaglandin production in the platelet dense tubular system.

J M Gerrard, J G White, G H Rao, D Townsend
PMCID: PMC2032323  PMID: 1266944

Abstract

Platelet production of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5,10-heptadecadienoic acid (PHD), two metabolites of the prostaglandin cyclic endoperoxides PGG2 and PGH2, was found in this investigation to occur primarily in a platelet microsomal fraction consisting almost exclusively of membranes. To further localize the membrane site of platelet prostaglandin biosynthesis, the present study has used a cytochemical technique employing 3,3'-diaminobenzidine as an oxidizable substrate. The reaction product was found to localize in the platelet dense tubular system. Formation of the reaction product was inhibited by aminotriazole. In similar concentrations, aminotriazole inhibited collagen and arachidonic acid aggregation, the second wave of ADP and epinephrine aggregation, but failed to inhibit aggregation by PGG2 and A23187. A study of the mechanism of action of aminotriazole revealed inhibition of formation of HHT and PHD. The results localize platelet prostaglandin biosynthesis to the membranes of the dense tubular system.

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297Figure 3 and 4
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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anggård E., Bohman S. O., Griffin J. E., 3rd, Larsson C., Maunsbach A. B. Subcellular localization of the prostaglandin system in the rabbit renal papilla. Acta Physiol Scand. 1972 Feb;84(2):231–246. doi: 10.1111/j.1748-1716.1972.tb05174.x. [DOI] [PubMed] [Google Scholar]
  2. Cavallo T. Fine structural localization of endogenous peroxidase activity in inner medullary interstitial cells of the rat kidney. Lab Invest. 1974 Nov;31(5):458–464. [PubMed] [Google Scholar]
  3. Clawson C. C., White J. G. Platelet interaction with bacteria. I. Reaction phases and effects of inhibitors. Am J Pathol. 1971 Nov;65(2):367–380. [PMC free article] [PubMed] [Google Scholar]
  4. Ebashi S., Endo M., Otsuki I. Control of muscle contraction. Q Rev Biophys. 1969 Nov;2(4):351–384. doi: 10.1017/s0033583500001190. [DOI] [PubMed] [Google Scholar]
  5. Gerrard J. M., White J. G., Krivit W. Proceedings: Effects of pH on arachidonic acid induced platelet aggregation. Thromb Diath Haemorrh. 1975 Nov 15;34(2):560–560. [PubMed] [Google Scholar]
  6. Gerrard J. M., White J. G., Rao G. H. Effects of the lonophore A23187 on the blood platelets II. Influence on ultrastructure. Am J Pathol. 1974 Nov;77(2):151–166. [PMC free article] [PubMed] [Google Scholar]
  7. Gerrard J. M., White J. G., Rao G. H., Krivit W., Witkop C. J., Jr Labile aggregation stimulating substance (LASS): the factor from storage pool deficient platelets correcting defective aggregation and release of aspirin treated normal platelets. Br J Haematol. 1975 Apr;29(4):657–665. doi: 10.1111/j.1365-2141.1975.tb02751.x. [DOI] [PubMed] [Google Scholar]
  8. Gerrard J. M., White J. G. The influence of aspirin and indomethacin on the platelet contractile wave. Am J Pathol. 1976 Mar;82(3):513–526. [PMC free article] [PubMed] [Google Scholar]
  9. Gerrard J. M., White J. G. The influence of prostaglandin endoperoxides on platelet ultrastructure. Am J Pathol. 1975 Aug;80(2):189–202. [PMC free article] [PubMed] [Google Scholar]
  10. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  11. Hamberg M., Samuelsson B. Oxygenation of unsaturated fatty acids by the vesicular gland of sheep. J Biol Chem. 1967 Nov 25;242(22):5344–5354. [PubMed] [Google Scholar]
  12. Hamberg M., Samuelsson B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3400–3404. doi: 10.1073/pnas.71.9.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hamberg M., Svensson J., Wakabayashi T., Samuelsson B. Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proc Natl Acad Sci U S A. 1974 Feb;71(2):345–349. doi: 10.1073/pnas.71.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Janszen F. H., Nugteren D. H. Histochemical localisation of prostaglandin synthetase. Histochemie. 1971;27(2):159–164. doi: 10.1007/BF00284957. [DOI] [PubMed] [Google Scholar]
  15. Kataoka K., Ramwell P. W., Jessup S. Prostaglandins: localization in subcellular particles of rat cerebral cortex. Science. 1967 Sep 8;157(3793):1187–1189. doi: 10.1126/science.157.3793.1187. [DOI] [PubMed] [Google Scholar]
  16. Nugteren D. H. Arachidonate lipoxygenase in blood platelets. Biochim Biophys Acta. 1975 Feb 20;380(2):299–307. doi: 10.1016/0005-2760(75)90016-8. [DOI] [PubMed] [Google Scholar]
  17. Panganamala R. V., Brownlee N. R., Sprecher H., Cornwell D. G. Evaluation of superoxide anion and singlet oxygen in the biosynthesis of prostaglandins from eicosa-8,11,14-trienoic acid. Prostaglandins. 1974 Jul 10;7(1):21–28. doi: 10.1016/s0090-6980(74)80074-2. [DOI] [PubMed] [Google Scholar]
  18. Panganamala R. V., Sharma H. M., Sprecher H., Geer J. C., Cornwell D. G. A suggested role for hydrogen peroxide in the biosynthesis of prostaglandins. Prostaglandins. 1974 Oct 10;8(1):3–11. doi: 10.1016/0090-6980(74)90031-8. [DOI] [PubMed] [Google Scholar]
  19. Silver M. J., Smith J. B., Ingerman C., Kocsis J. J. Arachidonic acid-induced human platelet aggregation and prostaglandin formation. Prostaglandins. 1973 Dec;4(6):863–875. doi: 10.1016/0090-6980(73)90121-4. [DOI] [PubMed] [Google Scholar]
  20. Smith J. B., Willis A. L. Aspirin selectively inhibits prostaglandin production in human platelets. Nat New Biol. 1971 Jun 23;231(25):235–237. doi: 10.1038/newbio231235a0. [DOI] [PubMed] [Google Scholar]
  21. Thamer G., Kommerell B. A radioimmunoassay to determine the subtypes D and Y of the hepatitis-B surface antigen. J Lab Clin Med. 1976 Apr;87(4):734–738. [PubMed] [Google Scholar]
  22. Vargaftig B. B., Tranier Y., Chignard M. Blockade by metal complexing agents and by catalase of the effects of arachidonic acid on platelets: relevance to the study of anti-inflammatory mechanisms. Eur J Pharmacol. 1975 Aug;33(1):19–29. doi: 10.1016/0014-2999(75)90133-8. [DOI] [PubMed] [Google Scholar]
  23. White J. G. Fine structural alterations induced in platelets by adenosine diphosphate. Blood. 1968 May;31(5):604–622. [PubMed] [Google Scholar]
  24. White J. G. Interaction of membrane systems in blood platelets. Am J Pathol. 1972 Feb;66(2):295–312. [PMC free article] [PubMed] [Google Scholar]
  25. Willis A. L., Kuhn D. C. A new potential mediator of arterial thrombosis whose biosynthesis is inhibited by aspirin. Prostaglandins. 1973 Jul;4(1):127–130. doi: 10.1016/0090-6980(73)90062-2. [DOI] [PubMed] [Google Scholar]

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