Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Apr;85(7):2334–2338. doi: 10.1073/pnas.85.7.2334

Receptor-mediated release of endothelium-derived relaxing factor and prostacyclin from bovine aortic endothelial cells is coupled.

G de Nucci 1, R J Gryglewski 1, T D Warner 1, J R Vane 1
PMCID: PMC279986  PMID: 2832851

Abstract

Bovine aortic endothelial cells were grown on microcarrier beads and were perfused with Krebs-Ringer solution. Endothelium-derived relaxing factor (EDRF) was bioassayed on a cascade of four strips of rabbit aorta, and prostacyclin was analyzed by RIA of 6-oxo-prostaglandin F1 alpha. The endothelial cells released EDRF and prostacyclin when stimulated with bradykinin and its analogues, or with ADP, ATP, arachidonic acid, and phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3). The detection of EDRF was potentiated by superoxide dismutase, and the relaxation of rabbit aortic strips induced by EDRF was antagonized by methylene blue. The release of EDRF and prostacyclin was inhibited by phorbol myristate acetate, R59022 (a diacylglycerol kinase inhibitor), and gentamycin. We suggest that the release of EDRF and prostacyclin is coupled and the initial common step is activation of a phospholipase C.

Full text

PDF
2334

Selected References

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

  1. Arnold W. P., Mittal C. K., Katsuki S., Murad F. Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3203–3207. doi: 10.1073/pnas.74.8.3203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell R. L., Kennerly D. A., Stanford N., Majerus P. W. Diglyceride lipase: a pathway for arachidonate release from human platelets. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3238–3241. doi: 10.1073/pnas.76.7.3238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  5. Blackwell G. J., Carnuccio R., Di Rosa M., Flower R. J., Parente L., Persico P. Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids. Nature. 1980 Sep 11;287(5778):147–149. doi: 10.1038/287147a0. [DOI] [PubMed] [Google Scholar]
  6. Blackwell G. J., Flower R. J., Nijkamp F. P., Vane J. R. Phospholipase A2 activity of guinea-pig isolated perfused lungs: stimulation, and inhibition by anti-inflammatory steroids. Br J Pharmacol. 1978 Jan;62(1):79–89. doi: 10.1111/j.1476-5381.1978.tb07009.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown K. D., Blakeley D. M., Hamon M. H., Laurie M. S., Corps A. N. Protein kinase C-mediated negative-feedback inhibition of unstimulated and bombesin-stimulated polyphosphoinositide hydrolysis in Swiss-mouse 3T3 cells. Biochem J. 1987 Aug 1;245(3):631–639. doi: 10.1042/bj2450631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cocks T. M., Angus J. A., Campbell J. H., Campbell G. R. Release and properties of endothelium-derived relaxing factor (EDRF) from endothelial cells in culture. J Cell Physiol. 1985 Jun;123(3):310–320. doi: 10.1002/jcp.1041230304. [DOI] [PubMed] [Google Scholar]
  9. Dale M. M., Penfield A. Comparison of the effects of indomethacin, RHC80267 and R59022 on superoxide production by 1,oleoyl-2,acetyl glycerol and A23187 in human neutrophils. Br J Pharmacol. 1987 Sep;92(1):63–68. doi: 10.1111/j.1476-5381.1987.tb11296.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Derian C. K., Moskowitz M. A. Polyphosphoinositide hydrolysis in endothelial cells and carotid artery segments. Bradykinin-2 receptor stimulation is calcium-independent. J Biol Chem. 1986 Mar 15;261(8):3831–3837. [PubMed] [Google Scholar]
  11. Forsberg E. J., Feuerstein G., Shohami E., Pollard H. B. Adenosine triphosphate stimulates inositol phospholipid metabolism and prostacyclin formation in adrenal medullary endothelial cells by means of P2-purinergic receptors. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5630–5634. doi: 10.1073/pnas.84.16.5630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  13. Förstermann U., Burgwitz K., Frölich J. C. Effects of nonsteroidal phospholipase inhibitors and glucocorticoids on endothelium-dependent relaxations of rabbit aorta induced by different agents. J Cardiovasc Pharmacol. 1987 Sep;10(3):356–364. doi: 10.1097/00005344-198709000-00016. [DOI] [PubMed] [Google Scholar]
  14. Gordon J. L. Extracellular ATP: effects, sources and fate. Biochem J. 1986 Jan 15;233(2):309–319. doi: 10.1042/bj2330309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gorman R. R., Bunting S., Miller O. V. Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins. 1977 Mar;13(3):377–388. doi: 10.1016/0090-6980(77)90018-1. [DOI] [PubMed] [Google Scholar]
  16. Gryglewski R. J., Moncada S., Palmer R. M. Bioassay of prostacyclin and endothelium-derived relaxing factor (EDRF) from porcine aortic endothelial cells. Br J Pharmacol. 1986 Apr;87(4):685–694. doi: 10.1111/j.1476-5381.1986.tb14586.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gryglewski R. J., Palmer R. M., Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1986 Apr 3;320(6061):454–456. doi: 10.1038/320454a0. [DOI] [PubMed] [Google Scholar]
  18. Hibbs J. B., Jr, Taintor R. R., Vavrin Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science. 1987 Jan 23;235(4787):473–476. doi: 10.1126/science.2432665. [DOI] [PubMed] [Google Scholar]
  19. Hong S. L., Deykin D. Activation of phospholipases A2 and C in pig aortic endothelial cells synthesizing prostacyclin. J Biol Chem. 1982 Jun 25;257(12):7151–7154. [PubMed] [Google Scholar]
  20. Houston D. A., Burnstock G., Vanhoutte P. M. Different P2-purinergic receptor subtypes of endothelium and smooth muscle in canine blood vessels. J Pharmacol Exp Ther. 1987 May;241(2):501–506. [PubMed] [Google Scholar]
  21. Ignarro L. J., Harbison R. G., Wood K. S., Kadowitz P. J. Dissimilarities between methylene blue and cyanide on relaxation and cyclic GMP formation in endothelium-intact intrapulmonary artery caused by nitrogen oxide-containing vasodilators and acetylcholine. J Pharmacol Exp Ther. 1986 Jan;236(1):30–36. [PubMed] [Google Scholar]
  22. Iyengar R., Stuehr D. J., Marletta M. A. Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6369–6373. doi: 10.1073/pnas.84.18.6369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jaffe E. A., Grulich J., Weksler B. B., Hampel G., Watanabe K. Correlation between thrombin-induced prostacyclin production and inositol trisphosphate and cytosolic free calcium levels in cultured human endothelial cells. J Biol Chem. 1987 Jun 25;262(18):8557–8565. [PubMed] [Google Scholar]
  24. Katsuki S., Arnold W., Mittal C., Murad F. Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. J Cyclic Nucleotide Res. 1977 Feb;3(1):23–35. [PubMed] [Google Scholar]
  25. Kojima I., Shibata H., Ogata E. Phorbol ester inhibits angiotensin-induced activation of phospholipase C in adrenal glomerulosa cells. Its implication in the sustained action of angiotensin. Biochem J. 1986 Jul 1;237(1):253–258. doi: 10.1042/bj2370253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lambert T. L., Kent R. S., Whorton A. R. Bradykinin stimulation of inositol polyphosphate production in porcine aortic endothelial cells. J Biol Chem. 1986 Nov 15;261(32):15288–15293. [PubMed] [Google Scholar]
  27. Lewis M. J., Henderson A. H. A phorbol ester inhibits the release of endothelium-derived relaxing factor. Eur J Pharmacol. 1987 Jun 4;137(2-3):167–171. doi: 10.1016/0014-2999(87)90218-4. [DOI] [PubMed] [Google Scholar]
  28. Lipsky J. J., Lietman P. S. Aminoglycoside inhibition of a renal phosphatidylinositol phospholipase C. J Pharmacol Exp Ther. 1982 Feb;220(2):287–292. [PubMed] [Google Scholar]
  29. Lückhoff A., Busse R., Winter I., Bassenge E. Characterization of vascular relaxant factor released from cultured endothelial cells. Hypertension. 1987 Mar;9(3):295–303. doi: 10.1161/01.hyp.9.3.295. [DOI] [PubMed] [Google Scholar]
  30. Majerus P. W., Connolly T. M., Deckmyn H., Ross T. S., Bross T. E., Ishii H., Bansal V. S., Wilson D. B. The metabolism of phosphoinositide-derived messenger molecules. Science. 1986 Dec 19;234(4783):1519–1526. doi: 10.1126/science.3024320. [DOI] [PubMed] [Google Scholar]
  31. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  32. Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
  33. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  34. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  35. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  36. Pinto A., Abraham N. G., Mullane K. M. Cytochrome P-450-dependent monooxygenase activity and endothelial-dependent relaxations induced by arachidonic acid. J Pharmacol Exp Ther. 1986 Feb;236(2):445–451. [PubMed] [Google Scholar]
  37. Prescott S. M., Majerus P. W. Characterization of 1,2-diacylglycerol hydrolysis in human platelets. Demonstration of an arachidonoyl-monoacylglycerol intermediate. J Biol Chem. 1983 Jan 25;258(2):764–769. [PubMed] [Google Scholar]
  38. Radomski M. W., Palmer R. M., Moncada S. The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol. 1987 Nov;92(3):639–646. doi: 10.1111/j.1476-5381.1987.tb11367.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ragab-Thomas J. M., Hullin F., Chap H., Douste-Blazy L. Pathways of arachidonic acid liberation in thrombin and calcium ionophore A23187-stimulated human endothelial cells: respective roles of phospholipids and triacylglycerol and evidence for diacylglycerol generation from phosphatidylcholine. Biochim Biophys Acta. 1987 Feb 23;917(3):388–397. doi: 10.1016/0005-2760(87)90117-2. [DOI] [PubMed] [Google Scholar]
  40. Rapoport R. M., Draznin M. B., Murad F. Endothelium-dependent relaxation in rat aorta may be mediated through cyclic GMP-dependent protein phosphorylation. Nature. 1983 Nov 10;306(5939):174–176. doi: 10.1038/306174a0. [DOI] [PubMed] [Google Scholar]
  41. Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
  42. Rittenhouse-Simmons S. Indomethacin-induced accumulation of diglyceride in activated human platelets. The role of diglyceride lipase. J Biol Chem. 1980 Mar 25;255(6):2259–2262. [PubMed] [Google Scholar]
  43. Rittenhouse-Simmons S. Production of diglyceride from phosphatidylinositol in activated human platelets. J Clin Invest. 1979 Apr;63(4):580–587. doi: 10.1172/JCI109339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Salmon J. A. A radioimmunoassay for 6-keto-prostaglandin F1alpha. Prostaglandins. 1978 Mar;15(3):383–397. doi: 10.1016/0090-6980(78)90122-3. [DOI] [PubMed] [Google Scholar]
  45. Smith C. D., Uhing R. J., Snyderman R. Nucleotide regulatory protein-mediated activation of phospholipase C in human polymorphonuclear leukocytes is disrupted by phorbol esters. J Biol Chem. 1987 May 5;262(13):6121–6127. [PubMed] [Google Scholar]
  46. Tateson J. E., Moncada S., Vane J. R. Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins. 1977 Mar;13(3):389–397. doi: 10.1016/0090-6980(77)90019-3. [DOI] [PubMed] [Google Scholar]
  47. Thomas G., Mostaghim R., Ramwell P. W. Endothelium dependent vascular relaxation by arginine containing polypeptides. Biochem Biophys Res Commun. 1986 Dec 15;141(2):446–451. doi: 10.1016/s0006-291x(86)80193-0. [DOI] [PubMed] [Google Scholar]
  48. VANE J. R. THE USE OF ISOLATED ORGANS FOR DETECTING ACTIVE SUBSTANCES IN THE CIRCULATING BLOOD. Br J Pharmacol Chemother. 1964 Oct;23:360–373. doi: 10.1111/j.1476-5381.1964.tb01592.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Whorton A. R., Young S. L., Data J. L., Barchowsky A., Kent R. S. Mechanism of bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells. Biochim Biophys Acta. 1982 Jul 20;712(1):79–87. doi: 10.1016/0005-2760(82)90087-x. [DOI] [PubMed] [Google Scholar]
  50. Yamanishi J., Takai Y., Kaibuchi K., Sano K., Castagna M., Nishizuka Y. Synergistic functions of phorbol ester and calcium in serotonin release from human platelets. Biochem Biophys Res Commun. 1983 Apr 29;112(2):778–786. doi: 10.1016/0006-291x(83)91529-2. [DOI] [PubMed] [Google Scholar]
  51. de Chaffoy de Courcelles D. C., Roevens P., Van Belle H. R 59 022, a diacylglycerol kinase inhibitor. Its effect on diacylglycerol and thrombin-induced C kinase activation in the intact platelet. J Biol Chem. 1985 Dec 15;260(29):15762–15770. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES