Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Aug;88(2):456–461. doi: 10.1172/JCI115325

An epoxygenase metabolite of arachidonic acid mediates angiotensin II-induced rises in cytosolic calcium in rabbit proximal tubule epithelial cells.

Z T Madhun 1, D A Goldthwait 1, D McKay 1, U Hopfer 1, J G Douglas 1
PMCID: PMC295359  PMID: 1650793

Abstract

Previous studies from this and other laboratories have shown that angiotensin II (AII) induces [Ca2+]i transients in proximal tubular epithelium independent of phospholipase C. AII also stimulates formation of 5,6-epoxyeicosatrienoic acid (5,6-EET) from arachidonic acid by a cytochrome P450 epoxygenase and decreases Na+ transport in the same concentration range. Because 5,6-EET mimics AII with regard to Na+ transport, it effects on calcium mobilization were evaluated. [Ca2+]i was measured by video microscopy with the fluorescent indicator fura-2 employing cultured rabbit proximal tubule. AII-induced [Ca2+]i transients were enhanced by arachidonic acid and attenuated by ketoconazole, an inhibitor of cytochrome P450 epoxygenases. Arachidonic acid also elicited a [Ca2+]i transient that was attenuated by ketoconazole. 5,6-EET augmented [Ca2+]i similar to that seen with AII, but was unaffected by ketoconazole. By contrast, the other regioisomers (8,9-, 11,12-, and 14,15-EET) were much less potent. [Ca2+]i transients resulted from influx through verapamil- and nifedipine-sensitive channels. These results suggest a novel mechanism for AII-induced Ca mobilization in proximal tubule involving cytochrome P450-dependent arachidonic acid metabolism and Ca influx through voltage-sensitive channels.

Full text

PDF
456

Selected References

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

  1. Alexander R. W., Brock T. A., Gimbrone M. A., Jr, Rittenhouse S. E. Angiotensin increases inositol trisphosphate and calcium in vascular smooth muscle. Hypertension. 1985 May-Jun;7(3 Pt 1):447–451. [PubMed] [Google Scholar]
  2. Capdevila J., Chacos N., Falck J. R., Manna S., Negro-Vilar A., Ojeda S. R. Novel hypothalamic arachidonate products stimulate somatostatin release from the median eminence. Endocrinology. 1983 Jul;113(1):421–423. doi: 10.1210/endo-113-1-421. [DOI] [PubMed] [Google Scholar]
  3. Cashman J. R., Hanks D., Weiner R. I. Epoxy derivatives of arachidonic acid are potent stimulators of prolactin secretion. Neuroendocrinology. 1987 Sep;46(3):246–251. doi: 10.1159/000124827. [DOI] [PubMed] [Google Scholar]
  4. Chung S. D., Alavi N., Livingston D., Hiller S., Taub M. Characterization of primary rabbit kidney cultures that express proximal tubule functions in a hormonally defined medium. J Cell Biol. 1982 Oct;95(1):118–126. doi: 10.1083/jcb.95.1.118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dominguez J. H., Snowdowne K. W., Freudenrich C. C., Brown T., Borle A. B. Intracellular messenger for action of angiotensin II on fluid transport in rabbit proximal tubule. Am J Physiol. 1987 Mar;252(3 Pt 2):F423–F428. doi: 10.1152/ajprenal.1987.252.3.F423. [DOI] [PubMed] [Google Scholar]
  6. Douglas J. G. Angiotensin receptor subtypes of the kidney cortex. Am J Physiol. 1987 Jul;253(1 Pt 2):F1–F7. doi: 10.1152/ajprenal.1987.253.1.F1. [DOI] [PubMed] [Google Scholar]
  7. Douglas J. G., Romero M., Hopfer U. Signaling mechanisms coupled to the angiotensin receptor of proximal tubular epithelium. Kidney Int Suppl. 1990 Nov;30:S43–S47. [PubMed] [Google Scholar]
  8. Fabiato A. Computer programs for calculating total from specified free or free from specified total ionic concentrations in aqueous solutions containing multiple metals and ligands. Methods Enzymol. 1988;157:378–417. doi: 10.1016/0076-6879(88)57093-3. [DOI] [PubMed] [Google Scholar]
  9. Falck J. R., Manna S., Moltz J., Chacos N., Capdevila J. Epoxyeicosatrienoic acids stimulate glucagon and insulin release from isolated rat pancreatic islets. Biochem Biophys Res Commun. 1983 Jul 29;114(2):743–749. doi: 10.1016/0006-291x(83)90843-4. [DOI] [PubMed] [Google Scholar]
  10. Fukuo K., Morimoto S., Koh E., Yukawa S., Tsuchiya H., Imanaka S., Yamamoto H., Onishi T., Kumahara Y. Effects of prostaglandins on the cytosolic free calcium concentration in vascular smooth muscle cells. Biochem Biophys Res Commun. 1986 Apr 14;136(1):247–252. doi: 10.1016/0006-291x(86)90901-0. [DOI] [PubMed] [Google Scholar]
  11. Griffin H. D., Hawthorne J. N. Calcium-activated hydrolysis of phosphatidyl-myo-inositol 4-phosphate and phosphatidyl-myo-inositol 4,5-bisphosphate in guinea-pig synaptosomes. Biochem J. 1978 Nov 15;176(2):541–552. doi: 10.1042/bj1760541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  13. Harris P. J., Young J. A. Dose-dependent stimulation and inhibition of proximal tubular sodium reabsorption by angiotensin II in the rat kidney. Pflugers Arch. 1977 Jan 17;367(3):295–297. doi: 10.1007/BF00581370. [DOI] [PubMed] [Google Scholar]
  14. Hausdorff W. P., Catt K. J. Activation of dihydropyridine-sensitive calcium channels and biphasic cytosolic calcium responses by angiotensin II in rat adrenal glomerulosa cells. Endocrinology. 1988 Dec;123(6):2818–2826. doi: 10.1210/endo-123-6-2818. [DOI] [PubMed] [Google Scholar]
  15. Imbert-Teboul M., Siaume S., Morel F. Sites of prostaglandin E2 (PGE2) synthesis along the rabbit nephron. Mol Cell Endocrinol. 1986 Apr;45(1):1–10. doi: 10.1016/0303-7207(86)90076-6. [DOI] [PubMed] [Google Scholar]
  16. Jim K., Hassid A., Sun F., Dunn M. J. Lipoxygenase activity in rat kidney glomeruli, glomerular epithelial cells, and cortical tubules. J Biol Chem. 1982 Sep 10;257(17):10294–10299. [PubMed] [Google Scholar]
  17. Liu F. Y., Cogan M. G. Angiotensin II stimulates early proximal bicarbonate absorption in the rat by decreasing cyclic adenosine monophosphate. J Clin Invest. 1989 Jul;84(1):83–91. doi: 10.1172/JCI114174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mene P., Dubyak G. R., Scarpa A., Dunn M. J. Stimulation of cytosolic free calcium and inositol phosphates by prostaglandins in cultured rat mesangial cells. Biochem Biophys Res Commun. 1987 Jan 30;142(2):579–586. doi: 10.1016/0006-291x(87)90313-5. [DOI] [PubMed] [Google Scholar]
  19. Naccache P. H., Sha'afi R. I., Borgeat P., Goetzl E. J. Mono- and dihydroxyeicosatetraenoic acids alter calcium homeostasis in rabbit neutrophils. J Clin Invest. 1981 May;67(5):1584–1587. doi: 10.1172/JCI110191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Negro-Vilar A., Snyder G. D., Falck J. R., Manna S., Chacos N., Capdevila J. Involvement of eicosanoids in release of oxytocin and vasopressin from the neural lobe of the rat pituitary. Endocrinology. 1985 Jun;116(6):2663–2668. doi: 10.1210/endo-116-6-2663. [DOI] [PubMed] [Google Scholar]
  21. Norman J., Badie-Dezfooly B., Nord E. P., Kurtz I., Schlosser J., Chaudhari A., Fine L. G. EGF-induced mitogenesis in proximal tubular cells: potentiation by angiotensin II. Am J Physiol. 1987 Aug;253(2 Pt 2):F299–F309. doi: 10.1152/ajprenal.1987.253.2.F299. [DOI] [PubMed] [Google Scholar]
  22. O'Flaherty J. T., Jacobson D., Redman J. Mechanism involved in the mobilization of neutrophil calcium by 5-hydroxyeicosatetraenoate. J Immunol. 1988 Jun 15;140(12):4323–4328. [PubMed] [Google Scholar]
  23. O'Flaherty J. T., Nishihira J. 5-Hydroxyeicosatetraenoate promotes Ca2+ and protein kinase C mobilization in neutrophils. Biochem Biophys Res Commun. 1987 Oct 29;148(2):575–581. doi: 10.1016/0006-291x(87)90915-6. [DOI] [PubMed] [Google Scholar]
  24. Ordway R. W., Walsh J. V., Jr, Singer J. J. Arachidonic acid and other fatty acids directly activate potassium channels in smooth muscle cells. Science. 1989 Jun 9;244(4909):1176–1179. doi: 10.1126/science.2471269. [DOI] [PubMed] [Google Scholar]
  25. Pfeilschifter J., Bauer C. Pertussis toxin abolishes angiotensin II-induced phosphoinositide hydrolysis and prostaglandin synthesis in rat renal mesangial cells. Biochem J. 1986 May 15;236(1):289–294. doi: 10.1042/bj2360289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Romero M. F., Hopfer U., Madhun Z. T., Zhou W., Douglas J. G. Angiotensin II actions in the rabbit proximal tubule. Angiotensin II mediated signaling mechanisms and electrolyte transport in the rabbit proximal tubule. Ren Physiol Biochem. 1991 Jul-Oct;14(4-5):199–207. doi: 10.1159/000173405. [DOI] [PubMed] [Google Scholar]
  27. Sakhrani L. M., Tessitore N., Massry S. G. Effect of calcium on transport characteristics of cultured proximal renal cells. Am J Physiol. 1985 Sep;249(3 Pt 2):F346–F355. doi: 10.1152/ajprenal.1985.249.3.F346. [DOI] [PubMed] [Google Scholar]
  28. Schuster V. L., Kokko J. P., Jacobson H. R. Angiotensin II directly stimulates sodium transport in rabbit proximal convoluted tubules. J Clin Invest. 1984 Feb;73(2):507–515. doi: 10.1172/JCI111237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Smith J. B., Smith L., Brown E. R., Barnes D., Sabir M. A., Davis J. S., Farese R. V. Angiotensin II rapidly increases phosphatidate-phosphoinositide synthesis and phosphoinositide hydrolysis and mobilizes intracellular calcium in cultured arterial muscle cells. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7812–7816. doi: 10.1073/pnas.81.24.7812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Snowdowne K. W., Rosenoer L., Yu E., Cashman J. R. Eicosanoids evoke the release of amylase and increase cytoplasmic calcium in rat parotid cells. Biochem Biophys Res Commun. 1989 May 30;161(1):379–384. doi: 10.1016/0006-291x(89)91608-2. [DOI] [PubMed] [Google Scholar]
  31. Snyder G. D., Capdevila J., Chacos N., Manna S., Falck J. R. Action of luteinizing hormone-releasing hormone: involvement of novel arachidonic acid metabolites. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3504–3507. doi: 10.1073/pnas.80.11.3504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Snyder G., Lattanzio F., Yadagiri P., Falck J. R., Capdevila J. 5,6-Epoxyeicosatrienoic acid mobilizes Ca2+ in anterior pituitary cells. Biochem Biophys Res Commun. 1986 Sep 30;139(3):1188–1194. doi: 10.1016/s0006-291x(86)80303-5. [DOI] [PubMed] [Google Scholar]
  33. Torres V. E., Northrup T. E., Edwards R. M., Shah S. V., Dousa T. P. Modulation of cyclic nucleotides in islated rat glomeruli: role of histamine, carbamylcholine, parathyroid hormone, and angiotensin-II. J Clin Invest. 1978 Dec;62(6):1334–1343. doi: 10.1172/JCI109254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wang T., Chan Y. L. The role of phosphoinositide turnover in mediating the biphasic effect of angiotensin II on renal tubular transport. J Pharmacol Exp Ther. 1991 Jan;256(1):309–317. [PubMed] [Google Scholar]
  35. Weinman E. J., Dubinsky W. P., Fisher K., Steplock D., Dinh Q., Chang L., Shenolikar S. Regulation of reconstituted renal Na+/H+ exchanger by calcium-dependent protein kinases. J Membr Biol. 1988 Aug;103(3):237–244. doi: 10.1007/BF01993983. [DOI] [PubMed] [Google Scholar]
  36. Welsh C., Dubyak G., Douglas J. G. Relationship between phospholipase C activation and prostaglandin E2 and cyclic adenosine monophosphate production in rabbit tubular epithelial cells. Effects of angiotensin, bradykinin, and arginine vasopressin. J Clin Invest. 1988 Mar;81(3):710–719. doi: 10.1172/JCI113376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Woodcock E. A., Johnston C. I. Inhibition of adenylate cyclase by angiotensin II in rat renal cortex. Endocrinology. 1982 Nov;111(5):1687–1691. doi: 10.1210/endo-111-5-1687. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES