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. 1994 Dec;78(12):921–926. doi: 10.1136/bjo.78.12.921

Localisation of thromboxane A2 receptors and the corresponding mRNAs in human eye tissue.

Z Chen 1, S Prasad 1, M Cynader 1
PMCID: PMC504994  PMID: 7819177

Abstract

Thromboxane A2 (TxA2) receptors in human eye sections were identified and localised using a potent TxA2 specific agonist, 125-iodinated 5-heptenoic acid 7-[3-[3-hydroxy-4-[4-(iodo-125I) phenoxy]-1-butenyl]-7- oxabicyclo[2.2.1]hept-2-yl]-,[1S-[1a,2a,(Z),3B(1E,3S*),4a]]-C23 H29 IO5 (125I-BOP) in a binding assay. TxA2 receptors were concentrated in several specific loci within ocular tissues, including the corneal epithelium, the ciliary processes, retina, and posterior ciliary arteries. In addition, we have used the method of in situ hybridisation to observe the distribution of TxA2 receptor mRNA. The distributions of both receptor binding sites and receptor mRNAs showed a close correlation. These studies employed film autoradiography which does not permit cellular resolution. In order to obtain enhanced cellular resolution and more detailed information about the localisation of the receptors and their corresponding mRNAs, emulsion autoradiography was used after ligand binding and in situ hybridisation. This approach showed further that TxA2 receptors are mainly concentrated on non-pigmented epithelial cells of the ciliary processes, on photoreceptors within the retina, and on endothelial cells of the posterior ciliary arteries. These results may be helpful for understanding the pathophysiological effects of TxA2 in the human eye.

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Selected References

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

  1. Ashby B. Effect of thromboxane antagonists on prostaglandin regulation of platelet adenylate cyclase. Second Messengers Phosphoproteins. 1988;12(5-6):241–250. [PubMed] [Google Scholar]
  2. Coleman R. A., Humphrey P. P., Kennedy I., Levy G. P., Lumley P. Comparison of the actions of U-46619, a prostaglandin H2-analogue, with those of prostaglandin H2 and thromboxane A2 on some isolated smooth muscle preparations. Br J Pharmacol. 1981 Jul;73(3):773–778. doi: 10.1111/j.1476-5381.1981.tb16814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  4. Halushka P. V., Mais D. E., Garvin M. Binding of a thromboxane A2/prostaglandin H2 receptor antagonist to guinea-pig platelets. Eur J Pharmacol. 1986 Nov 12;131(1):49–54. doi: 10.1016/0014-2999(86)90514-5. [DOI] [PubMed] [Google Scholar]
  5. Halushka P. V., Mais D. E., Mayeux P. R., Morinelli T. A. Thromboxane, prostaglandin and leukotriene receptors. Annu Rev Pharmacol Toxicol. 1989;29:213–239. doi: 10.1146/annurev.pa.29.040189.001241. [DOI] [PubMed] [Google Scholar]
  6. Hayashi S., Park M. K., Kuehl T. J. Effects of prostaglandins and arachidonic acid on baboon cerebral and mesenteric arteries. Prostaglandins. 1986 Oct;32(4):587–596. doi: 10.1016/0090-6980(86)90040-7. [DOI] [PubMed] [Google Scholar]
  7. Hirata M., Hayashi Y., Ushikubi F., Yokota Y., Kageyama R., Nakanishi S., Narumiya S. Cloning and expression of cDNA for a human thromboxane A2 receptor. Nature. 1991 Feb 14;349(6310):617–620. doi: 10.1038/349617a0. [DOI] [PubMed] [Google Scholar]
  8. Jones R. L., Peesapati V., Wilson N. H. Antagonism of the thromboxane-sensitive contractile systems of the rabbit aorta, dog saphenous vein and guinea-pig trachea. Br J Pharmacol. 1982 Jul;76(3):423–438. doi: 10.1111/j.1476-5381.1982.tb09236.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kawahara Y., Yamanishi J., Furuta Y., Kaibuchi K., Takai Y., Fukuzaki H. Elevation of cytoplasmic free calcium concentration by stable thromboxane A2 analogue in human platelets. Biochem Biophys Res Commun. 1983 Dec 28;117(3):663–669. doi: 10.1016/0006-291x(83)91648-0. [DOI] [PubMed] [Google Scholar]
  10. Lefer A. M. Eicosanoids as mediators of ischemia and shock. Fed Proc. 1985 Feb;44(2):275–280. [PubMed] [Google Scholar]
  11. Lewy R. I., Wiener L., Walinsky P., Lefer A. M., Silver M. J., Smith J. B. Thromboxane release during pacing-induced angina pectoris: possible vasoconstrictor influence on the coronary vasculature. Circulation. 1980 Jun;61(6):1165–1171. doi: 10.1161/01.cir.61.6.1165. [DOI] [PubMed] [Google Scholar]
  12. Mais D. E., Kochel P. J., Saussy D. L., Jr, Halushka P. V. Binding of an 125I-labeled thromboxane A2/prostaglandin H2 receptor antagonist to washed canine platelets. Mol Pharmacol. 1985 Aug;28(2):163–169. [PubMed] [Google Scholar]
  13. Masuda A., Mais D. E., Oatis J. E., Jr, Halushka P. V. Platelet and vascular thromboxane A2/prostaglandin H2 receptors. Evidence for different subclasses in the rat. Biochem Pharmacol. 1991 Jul 15;42(3):537–544. doi: 10.1016/0006-2952(91)90316-w. [DOI] [PubMed] [Google Scholar]
  14. Matsuo T., Cynader M. S. Localisation of prostaglandin F2 alpha and E2 binding sites in the human eye. Br J Ophthalmol. 1992 Apr;76(4):210–213. doi: 10.1136/bjo.76.4.210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mitchell J. R. Clinical aspects of the arachidonic acid--thromboxane pathway. Br Med Bull. 1983 Jul;39(3):289–295. doi: 10.1093/oxfordjournals.bmb.a071836. [DOI] [PubMed] [Google Scholar]
  16. Naka M., Mais D. E., Morinelli T. A., Hamanaka N., Oatis J. E., Jr, Halushka P. V. 7-[(1R,2S,3S,5R)-6,6-dimethyl-3-(4- iodobenzenesulfonylamino)bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoic acid: a novel high-affinity radiolabeled antagonist for platelet thromboxane A2/prostaglandin H2 receptors. J Pharmacol Exp Ther. 1992 Aug;262(2):632–637. [PubMed] [Google Scholar]
  17. Narumiya S., Okuma M., Ushikubi F. Binding of a radioiodinated 13-azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species. Br J Pharmacol. 1986 Jun;88(2):323–331. doi: 10.1111/j.1476-5381.1986.tb10208.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Okwu A. K., Ullian M. E., Halushka P. V. Homologous desensitization of human platelet thromboxane A2/prostaglandin H2 receptors. J Pharmacol Exp Ther. 1992 Jul;262(1):238–245. [PubMed] [Google Scholar]
  19. Pararajasegaram G., Sevanian A., Rao N. A. Suppression of S antigen-induced uveitis by vitamin E supplementation. Ophthalmic Res. 1991;23(3):121–127. doi: 10.1159/000267110. [DOI] [PubMed] [Google Scholar]
  20. Stjernschantz J., Nilsson S. F., Astin M. Vasodynamic and angiogenic effects of eicosanoids in the eye. Prog Clin Biol Res. 1989;312:155–170. [PubMed] [Google Scholar]
  21. Stjernschantz J., Nilsson S. F., Astin M. Vasodynamic and angiogenic effects of eicosanoids in the eye. Prog Clin Biol Res. 1989;312:155–170. [PubMed] [Google Scholar]
  22. Sung C. P., Arleth A. J., Berkowitz B. A. Endothelial thromboxane receptors: biochemical characterization and functional implications. Biochem Biophys Res Commun. 1989 Jan 16;158(1):326–333. doi: 10.1016/s0006-291x(89)80216-5. [DOI] [PubMed] [Google Scholar]
  23. Taube C., Hoffman P., Förster W. Enhanced thromboxane production in the aorta of spontaneously hypertensive rats in vitro. Prostaglandins Leukot Med. 1982 Oct;9(4):411–413. doi: 10.1016/0262-1746(82)90097-x. [DOI] [PubMed] [Google Scholar]
  24. Ushikubi F., Nakajima M., Hirata M., Okuma M., Fujiwara M., Narumiya S. Purification of the thromboxane A2/prostaglandin H2 receptor from human blood platelets. J Biol Chem. 1989 Oct 5;264(28):16496–16501. [PubMed] [Google Scholar]
  25. Whittle B. J., Moncada S. Pharmacological interactions between prostacyclin and thromboxanes. Br Med Bull. 1983 Jul;39(3):232–238. doi: 10.1093/oxfordjournals.bmb.a071825. [DOI] [PubMed] [Google Scholar]
  26. Woodward D. F., Nieves A. L., Williams L. S. Thromboxane A2-mimetics are potent microvascular permeability factors in the conjunctiva. J Pharmacol Exp Ther. 1990 Oct;255(1):23–27. [PubMed] [Google Scholar]

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