Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Dec;80(6):1561–1570. doi: 10.1172/JCI113242

Effects of protein kinase C activation on sodium, potassium, chloride, and total CO2 transport in the rabbit cortical collecting tubule.

S R Hays 1, M Baum 1, J P Kokko 1
PMCID: PMC442424  PMID: 3680514

Abstract

Several hormones induce phosphatidylinositol turnover in cell membranes and thus activate protein kinase C. Activation of protein kinase C can, in turn, have effects on epithelial transport. These experiments were designed to investigate the effects of two activators of protein kinase C, phorbol 12-myristate,13-acetate (PMA) and L-alpha-1,2-dioctanoylglycerol (L-alpha-1,2-DOG), and two inactive analogues, 4 alpha-phorbol and 4-O-methyl phorbol 12-myristate,13-acetate, on sodium, potassium, chloride, and total CO2 transport in the rabbit cortical collecting tubule. Utilizing in vitro microperfusion techniques, we found that activation of protein kinase C with either PMA or L-alpha-1,2-DOG significantly inhibited net sodium absorption, net potassium secretion and transepithelial voltage in a dose-dependent manner. There was no effect on net chloride or total CO2 transport. In contrast, the inactive phorbol analogues did not alter either sodium or potassium transport. These studies demonstrate that in the rabbit cortical collecting tubule sodium and potassium transport can be inhibited by compounds known to activate proteins kinase C. Thus, hormones that induce phosphatidylinositol turnover in the rabbit cortical collecting tubule may lead to inhibition of sodium transport by activation of protein kinase C.

Full text

PDF
1561

Selected References

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

  1. Ahn J., Chang E. B., Field M. Phorbol ester inhibition of Na-H exchange in rabbit proximal colon. Am J Physiol. 1985 Nov;249(5 Pt 1):C527–C530. doi: 10.1152/ajpcell.1985.249.5.C527. [DOI] [PubMed] [Google Scholar]
  2. Baraban J. M., Snyder S. H., Alger B. E. Protein kinase C regulates ionic conductance in hippocampal pyramidal neurons: electrophysiological effects of phorbol esters. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2538–2542. doi: 10.1073/pnas.82.8.2538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bell R. M. Protein kinase C activation by diacylglycerol second messengers. Cell. 1986 Jun 6;45(5):631–632. doi: 10.1016/0092-8674(86)90774-9. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Besterman J. M., Cuatrecasas P. Phorbol esters rapidly stimulate amiloride-sensitive Na+/H+ exchange in a human leukemic cell line. J Cell Biol. 1984 Jul;99(1 Pt 1):340–343. doi: 10.1083/jcb.99.1.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burg M. B. Perfusion of isolated renal tubules. Yale J Biol Med. 1972 Jun-Aug;45(3-4):321–326. [PMC free article] [PubMed] [Google Scholar]
  7. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  8. Chang E. B., Wang N. S., Rao M. C. Phorbol ester stimulation of active anion secretion in intestine. Am J Physiol. 1985 Sep;249(3 Pt 1):C356–C361. doi: 10.1152/ajpcell.1985.249.3.C356. [DOI] [PubMed] [Google Scholar]
  9. Civan M. M., Rubenstein D., Mauro T., O'Brien T. G. Effects of tumor promoters on sodium ion transport across frog skin. Am J Physiol. 1985 May;248(5 Pt 1):C457–C465. doi: 10.1152/ajpcell.1985.248.5.C457. [DOI] [PubMed] [Google Scholar]
  10. Curry S. H., Brown E. A., Kuck H., Cassin S. Preparation and stability of indomethacin solutions. Can J Physiol Pharmacol. 1982 Jul;60(7):988–992. doi: 10.1139/y82-139. [DOI] [PubMed] [Google Scholar]
  11. Dascal N., Lotan I., Gillo B., Lester H. A., Lass Y. Acetylcholine and phorbol esters inhibit potassium currents evoked by adenosine and cAMP in Xenopus oocytes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):6001–6005. doi: 10.1073/pnas.82.17.6001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Davis R. J., Ganong B. R., Bell R. M., Czech M. P. Structural requirements for diacylglycerols to mimic tumor-promoting phobol diester action on the epidermal growth factor receptor. J Biol Chem. 1985 May 10;260(9):5315–5322. [PubMed] [Google Scholar]
  13. Dicker P., Rozengurt E. Phorbol ester stimulation of Na influx and Na-K pump activity in Swiss 3T3 cells. Biochem Biophys Res Commun. 1981 May 15;100(1):433–441. doi: 10.1016/s0006-291x(81)80115-5. [DOI] [PubMed] [Google Scholar]
  14. Donowitz M., Cheng H. Y., Sharp G. W. Effects of phorbol esters on sodium and chloride transport in rat colon. Am J Physiol. 1986 Oct;251(4 Pt 1):G509–G517. doi: 10.1152/ajpgi.1986.251.4.G509. [DOI] [PubMed] [Google Scholar]
  15. Fondacaro J. D., Henderson L. S. Evidence for protein kinase C as a regulator of intestinal electrolyte transport. Am J Physiol. 1985 Sep;249(3 Pt 1):G422–G426. doi: 10.1152/ajpgi.1985.249.3.G422. [DOI] [PubMed] [Google Scholar]
  16. Greene D. A., Lattimer S. A. Protein kinase C agonists acutely normalize decreased ouabain-inhibitable respiration in diabetic rabbit nerve. Implications for (Na,K)-ATPase regulation and diabetic complications. Diabetes. 1986 Feb;35(2):242–245. doi: 10.2337/diab.35.2.242. [DOI] [PubMed] [Google Scholar]
  17. Grinstein S., Cohen S., Goetz J. D., Rothstein A., Gelfand E. W. Characterization of the activation of Na+/H+ exchange in lymphocytes by phorbol esters: change in cytoplasmic pH dependence of the antiport. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1429–1433. doi: 10.1073/pnas.82.5.1429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hammerman M. R., Rogers S., Morrissey J. J., Gavin J. R., 3rd Phorbol ester-stimulated phosphorylation of basolateral membranes from canine kidney. Am J Physiol. 1986 Jun;250(6 Pt 2):F1073–F1081. doi: 10.1152/ajprenal.1986.250.6.F1073. [DOI] [PubMed] [Google Scholar]
  19. Hanley M. J., Kokko J. P. Study of chloride transport across the rabbit cortical collecting tubule. J Clin Invest. 1978 Jul;62(1):39–44. doi: 10.1172/JCI109111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hays S., Kokko J. P., Jacobson H. R. Hormonal regulation of proton secretion in rabbit medullary collecting duct. J Clin Invest. 1986 Nov;78(5):1279–1286. doi: 10.1172/JCI112712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Holt W. F., Lechene C. ADH-PGE2 interactions in cortical collecting tubule. I. Depression of sodium transport. Am J Physiol. 1981 Oct;241(4):F452–F460. doi: 10.1152/ajprenal.1981.241.4.F452. [DOI] [PubMed] [Google Scholar]
  22. Jacobson H. R. Effects of CO2 and acetazolamide on bicarbonate and fluid transport in rabbit proximal tubules. Am J Physiol. 1981 Jan;240(1):F54–F62. doi: 10.1152/ajprenal.1981.240.1.F54. [DOI] [PubMed] [Google Scholar]
  23. Koeppen B. M., Biagi B. A., Giebisch G. H. Intracellular microelectrode characterization of the rabbit cortical collecting duct. Am J Physiol. 1983 Jan;244(1):F35–F47. doi: 10.1152/ajprenal.1983.244.1.F35. [DOI] [PubMed] [Google Scholar]
  24. Kraft A. S., Anderson W. B. Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane. Nature. 1983 Feb 17;301(5901):621–623. doi: 10.1038/301621a0. [DOI] [PubMed] [Google Scholar]
  25. Lynch C. J., Wilson P. B., Blackmore P. F., Exton J. H. The hormone-sensitive hepatic Na+-pump. Evidence for regulation by diacylglycerol and tumor promoters. J Biol Chem. 1986 Nov 5;261(31):14551–14556. [PubMed] [Google Scholar]
  26. McKinney T. D., Burg M. B. Bicarbonate transport by rabbit cortical collecting tubules. Effect of acid and alkali loads in vivo on transport in vitro. J Clin Invest. 1977 Sep;60(3):766–768. doi: 10.1172/JCI108830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mellas J., Hammerman M. R. Phorbol ester-induced alkalinization of canine renal proximal tubular cells. Am J Physiol. 1986 Mar;250(3 Pt 2):F451–F459. doi: 10.1152/ajprenal.1986.250.3.F451. [DOI] [PubMed] [Google Scholar]
  28. Nishizuka Y. Turnover of inositol phospholipids and signal transduction. Science. 1984 Sep 21;225(4668):1365–1370. doi: 10.1126/science.6147898. [DOI] [PubMed] [Google Scholar]
  29. O'Brien T. G., Krzeminski K. Phorbol ester inhibits furosemide-sensitive potassium transport in BALB/c 3T3 preadipose cells. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4334–4338. doi: 10.1073/pnas.80.14.4334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ohuchi K., Levine L. Stimulation of prostaglandin synthesis by tumor-promoting phorbol-12, 13-diesters in canine kidney (MDCK) cells. Cycloheximide inhibits the stimulated prostaglandin synthesis, deacylation of lipids, and morphological changes. J Biol Chem. 1978 Jul 10;253(13):4783–4790. [PubMed] [Google Scholar]
  31. Olsnes S., Tønnessen T. I., Sandvig K. pH-regulated anion antiport in nucleated mammalian cells. J Cell Biol. 1986 Mar;102(3):967–971. doi: 10.1083/jcb.102.3.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sansom S. C., Weinman E. J., O'Neil R. G. Microelectrode assessment of chloride-conductive properties of cortical collecting duct. Am J Physiol. 1984 Aug;247(2 Pt 2):F291–F302. doi: 10.1152/ajprenal.1984.247.2.F291. [DOI] [PubMed] [Google Scholar]
  33. Schafer J. A., Troutman S. L., Andreoli T. E. Volume reabsorption, transepithelial potential differences, and ionic permeability properties in mammalian superficial proximal straight tubules. J Gen Physiol. 1974 Nov;64(5):582–607. doi: 10.1085/jgp.64.5.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schlondorff D., Levine S. D. Inhibition of vasopressin-stimulated water flow in toad bladder by phorbol myristate acetate, dioctanoylglycerol, and RHC-80267. Evidence for modulation of action of vasopressin by protein kinase C. J Clin Invest. 1985 Sep;76(3):1071–1078. doi: 10.1172/JCI112060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schuster V. L., Kokko J. P., Jacobson H. R. Interactions of lysyl-bradykinin and antidiuretic hormone in the rabbit cortical collecting tubule. J Clin Invest. 1984 Jun;73(6):1659–1667. doi: 10.1172/JCI111372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schuster V. L. Mechanism of bradykinin, ADH, and cAMP interaction in rabbit cortical collecting duct. Am J Physiol. 1985 Nov;249(5 Pt 2):F645–F653. doi: 10.1152/ajprenal.1985.249.5.F645. [DOI] [PubMed] [Google Scholar]
  37. Star R. A., Burg M. B., Knepper M. A. Bicarbonate secretion and chloride absorption by rabbit cortical collecting ducts. Role of chloride/bicarbonate exchange. J Clin Invest. 1985 Sep;76(3):1123–1130. doi: 10.1172/JCI112067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Stokes J. B., Kokko J. P. Inhibition of sodium transport by prostaglandin E2 across the isolated, perfused rabbit collecting tubule. J Clin Invest. 1977 Jun;59(6):1099–1104. doi: 10.1172/JCI108733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stoner L. C., Burg M. B., Orloff J. Ion transport in cortical collecting tubule; effect of amiloride. Am J Physiol. 1974 Aug;227(2):453–459. doi: 10.1152/ajplegacy.1974.227.2.453. [DOI] [PubMed] [Google Scholar]
  40. Streb H., Irvine R. F., Berridge M. J., Schulz I. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature. 1983 Nov 3;306(5938):67–69. doi: 10.1038/306067a0. [DOI] [PubMed] [Google Scholar]
  41. Takai Y., Kishimoto A., Inoue M., Nishizuka Y. Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. I. Purification and characterization of an active enzyme from bovine cerebellum. J Biol Chem. 1977 Nov 10;252(21):7603–7609. [PubMed] [Google Scholar]
  42. Tapley P. M., Murray A. W. Modulation of Ca2+-activated, phospholipid-dependent protein kinase in platelets treated with a tumor-promoting phorbol ester. Biochem Biophys Res Commun. 1984 Jul 18;122(1):158–164. doi: 10.1016/0006-291x(84)90453-4. [DOI] [PubMed] [Google Scholar]
  43. Vara F., Schneider J. A., Rozengurt E. Ionic responses rapidly elicited by activation of protein kinase C in quiescent Swiss 3T3 cells. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2384–2388. doi: 10.1073/pnas.82.8.2384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yanase M., Handler J. S. Activators of protein kinase C inhibit sodium transport in A6 epithelia. Am J Physiol. 1986 Mar;250(3 Pt 1):C517–C522. doi: 10.1152/ajpcell.1986.250.3.C517. [DOI] [PubMed] [Google Scholar]

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

RESOURCES