Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Aug 1;98(3):662–670. doi: 10.1172/JCI118837

Expression of type II cGMP-dependent protein kinase in rat kidney is regulated by dehydration and correlated with renin gene expression.

S Gambaryan 1, C Häusler 1, T Markert 1, D Pöhler 1, T Jarchau 1, U Walter 1, W Haase 1, A Kurtz 1, S M Lohmann 1
PMCID: PMC507475  PMID: 8698857

Abstract

cGMP-based regulatory systems are vital for counteracting the renin-angiotensin system (RAS) which promotes volume expansion and high blood pressure. Natriuretic peptides and nitric oxide acting through their second messenger cGMP normally increase natriuresis and diuresis, and regulate renin release; however, the severe pathological state of cardiac heart failure is characterized by elevated levels of atrial natriuretic peptide that are no longer able to effectively oppose exaggerated RAS effects. There is presently limited information on the intracellular effectors of cGMP actions in the kidney. Recently we reported the cloning of the cDNA for type II cGMP-dependent protein kinase (cGK II), which is highly enriched in intestinal mucosa but was also detected for the first time in kidney. In the present study, cGK II was localized to juxtaglomerular (JG) cells, the ascending thin limb (ATL), and to a lesser extent the brush border of proximal tubules. An activator of renin gene expression, the angiotensin II type I receptor inhibitor, losartan, increased cGK II mRNA and protein three to fourfold in JG cells. In other experiments, water deprivation increased cGK II mRNA and protein three to fourfold in the inner medulla where both cGK II, and a kidney specific CI- channel shown by others to be regulated by dehydration, are localized in the ATL. Whereas additional data suggest that cGK I may primarily mediate cGMP-related changes in renal hemodynamics, cGK II may regulate renin release and ATL ion transport.

Full Text

The Full Text of this article is available as a PDF (602.8 KB).

Selected References

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

  1. Abassi Z. A., Kelly G., Golomb E., Klein H., Keiser H. R. Losartan improves the natriuretic response to ANF in rats with high-output heart failure. J Pharmacol Exp Ther. 1994 Jan;268(1):224–230. [PubMed] [Google Scholar]
  2. Biel M., Zong X., Hofmann F. Molecular diversity of cyclic nucleotide-gated cation channels. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):1–10. doi: 10.1007/BF00168909. [DOI] [PubMed] [Google Scholar]
  3. Butt E., Geiger J., Jarchau T., Lohmann S. M., Walter U. The cGMP-dependent protein kinase--gene, protein, and function. Neurochem Res. 1993 Jan;18(1):27–42. doi: 10.1007/BF00966920. [DOI] [PubMed] [Google Scholar]
  4. Büchler W., Meinecke M., Chakraborty T., Jahnsen T., Walter U., Lohmann S. M. Regulation of gene expression by transfected subunits of cAMP-dependent protein kinase. Eur J Biochem. 1990 Mar 10;188(2):253–259. doi: 10.1111/j.1432-1033.1990.tb15397.x. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Cornwell T. L., Lincoln T. M. Regulation of intracellular Ca2+ levels in cultured vascular smooth muscle cells. Reduction of Ca2+ by atriopeptin and 8-bromo-cyclic GMP is mediated by cyclic GMP-dependent protein kinase. J Biol Chem. 1989 Jan 15;264(2):1146–1155. [PubMed] [Google Scholar]
  7. Darvish N., Winaver J., Dagan D. A novel cGMP-activated Cl- channel in renal proximal tubules. Am J Physiol. 1995 Feb;268(2 Pt 2):F323–F329. doi: 10.1152/ajprenal.1995.268.2.F323. [DOI] [PubMed] [Google Scholar]
  8. Draijer R., Vaandrager A. B., Nolte C., de Jonge H. R., Walter U., van Hinsbergh V. W. Expression of cGMP-dependent protein kinase I and phosphorylation of its substrate, vasodilator-stimulated phosphoprotein, in human endothelial cells of different origin. Circ Res. 1995 Nov;77(5):897–905. doi: 10.1161/01.res.77.5.897. [DOI] [PubMed] [Google Scholar]
  9. Eigenthaler M., Ullrich H., Geiger J., Horstrup K., Hönig-Liedl P., Wiebecke D., Walter U. Defective nitrovasodilator-stimulated protein phosphorylation and calcium regulation in cGMP-dependent protein kinase-deficient human platelets of chronic myelocytic leukemia. J Biol Chem. 1993 Jun 25;268(18):13526–13531. [PubMed] [Google Scholar]
  10. Elalouf J. M., Buhler J. M., Tessiot C., Bellanger A. C., Dublineau I., de Rouffignac C. Predominant expression of beta 1-adrenergic receptor in the thick ascending limb of rat kidney. Absolute mRNA quantitation by reverse transcription and polymerase chain reaction. J Clin Invest. 1993 Jan;91(1):264–272. doi: 10.1172/JCI116180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Elsner D., Muders F., Müntze A., Kromer E. P., Forssmann W. G., Riegger G. A. Efficacy of prolonged infusion of urodilatin [ANP-(95-126)] in patients with congestive heart failure. Am Heart J. 1995 Apr;129(4):766–773. doi: 10.1016/0002-8703(95)90328-3. [DOI] [PubMed] [Google Scholar]
  12. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. French P. J., Bijman J., Edixhoven M., Vaandrager A. B., Scholte B. J., Lohmann S. M., Nairn A. C., de Jonge H. R. Isotype-specific activation of cystic fibrosis transmembrane conductance regulator-chloride channels by cGMP-dependent protein kinase II. J Biol Chem. 1995 Nov 3;270(44):26626–26631. doi: 10.1074/jbc.270.44.26626. [DOI] [PubMed] [Google Scholar]
  14. Garcia N. H., Garvin J. L. ANF and angiotensin II interact via kinases in the proximal straight tubule. Am J Physiol. 1995 Apr;268(4 Pt 2):F730–F735. doi: 10.1152/ajprenal.1995.268.4.F730. [DOI] [PubMed] [Google Scholar]
  15. Garvin J. L. Inhibition of Jv by ANF in rat proximal straight tubules requires angiotensin. Am J Physiol. 1989 Nov;257(5 Pt 2):F907–F911. doi: 10.1152/ajprenal.1989.257.5.F907. [DOI] [PubMed] [Google Scholar]
  16. Greenberg S. G., He X. R., Schnermann J. B., Briggs J. P. Effect of nitric oxide on renin secretion. I. Studies in isolated juxtaglomerular granular cells. Am J Physiol. 1995 May;268(5 Pt 2):F948–F952. doi: 10.1152/ajprenal.1995.268.5.F948. [DOI] [PubMed] [Google Scholar]
  17. Gudi T., Huvar I., Meinecke M., Lohmann S. M., Boss G. R., Pilz R. B. Regulation of gene expression by cGMP-dependent protein kinase. Transactivation of the c-fos promoter. J Biol Chem. 1996 Mar 1;271(9):4597–4600. doi: 10.1074/jbc.271.9.4597. [DOI] [PubMed] [Google Scholar]
  18. Guzman N. J., Fang M. Z., Tang S. S., Ingelfinger J. R., Garg L. C. Autocrine inhibition of Na+/K(+)-ATPase by nitric oxide in mouse proximal tubule epithelial cells. J Clin Invest. 1995 May;95(5):2083–2088. doi: 10.1172/JCI117895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. He X. R., Greenberg S. G., Briggs J. P., Schnermann J. B. Effect of nitric oxide on renin secretion. II. Studies in the perfused juxtaglomerular apparatus. Am J Physiol. 1995 May;268(5 Pt 2):F953–F959. doi: 10.1152/ajprenal.1995.268.5.F953. [DOI] [PubMed] [Google Scholar]
  20. Hess R., Kuhn M., Schulz-Knappe P., Raida M., Fuchs M., Klodt J., Adermann K., Kaever V., Cetin Y., Forssmann W. G. GCAP-II: isolation and characterization of the circulating form of human uroguanylin. FEBS Lett. 1995 Oct 23;374(1):34–38. doi: 10.1016/0014-5793(95)01075-p. [DOI] [PubMed] [Google Scholar]
  21. Hirsch J., Schlatter E. K+ channels in the basolateral membrane of rat cortical collecting duct are regulated by a cGMP-dependent protein kinase. Pflugers Arch. 1995 Jan;429(3):338–344. doi: 10.1007/BF00374148. [DOI] [PubMed] [Google Scholar]
  22. Holmer S., Eckardt K. U., Aedtner O., LeHir M., Schricker K., Hamann M., Götz K., Riegger G., Moll W., Kurtz A. Which factor mediates reno-renal control of renin gene expression? J Hypertens. 1993 Oct;11(10):1011–1019. doi: 10.1097/00004872-199310000-00003. [DOI] [PubMed] [Google Scholar]
  23. Jakob G., Mair J., Pichler M., Puschendorf B. Ergometric exercise testing and sensitivity of cyclic guanosine 3',5'-monophosphate (cGMP) in diagnosing asymptomatic left ventricular dysfunction. Br Heart J. 1995 Feb;73(2):145–150. doi: 10.1136/hrt.73.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jarchau T., Häusler C., Markert T., Pöhler D., Vanderkerckhove J., De Jonge H. R., Lohmann S. M., Walter U. Cloning, expression, and in situ localization of rat intestinal cGMP-dependent protein kinase II. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9426–9430. doi: 10.1073/pnas.91.20.9426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Joyce N. C., DeCamilli P., Lohmann S. M., Walter U. cGMP-dependent protein kinase is present in high concentrations in contractile cells of the kidney vasculature. J Cyclic Nucleotide Protein Phosphor Res. 1986;11(3):191–198. [PubMed] [Google Scholar]
  26. Kang P. M., Landau A. J., Eberhardt R. T., Frishman W. H. Angiotensin II receptor antagonists: a new approach to blockade of the renin-angiotensin system. Am Heart J. 1994 May;127(5):1388–1401. doi: 10.1016/0002-8703(94)90061-2. [DOI] [PubMed] [Google Scholar]
  27. Kurtz A. Cellular control of renin secretion. Rev Physiol Biochem Pharmacol. 1989;113:1–40. doi: 10.1007/BFb0032674. [DOI] [PubMed] [Google Scholar]
  28. Kurtz A., Della Bruna R., Pfeilschifter J., Taugner R., Bauer C. Atrial natriuretic peptide inhibits renin release from juxtaglomerular cells by a cGMP-mediated process. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4769–4773. doi: 10.1073/pnas.83.13.4769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kurtz A., Penner R. Angiotensin II induces oscillations of intracellular calcium and blocks anomalous inward rectifying potassium current in mouse renal juxtaglomerular cells. Proc Natl Acad Sci U S A. 1989 May;86(9):3423–3427. doi: 10.1073/pnas.86.9.3423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Light D. B., Corbin J. D., Stanton B. A. Dual ion-channel regulation by cyclic GMP and cyclic GMP-dependent protein kinase. Nature. 1990 Mar 22;344(6264):336–339. doi: 10.1038/344336a0. [DOI] [PubMed] [Google Scholar]
  31. Markert T., Vaandrager A. B., Gambaryan S., Pöhler D., Häusler C., Walter U., De Jonge H. R., Jarchau T., Lohmann S. M. Endogenous expression of type II cGMP-dependent protein kinase mRNA and protein in rat intestine. Implications for cystic fibrosis transmembrane conductance regulator. J Clin Invest. 1995 Aug;96(2):822–830. doi: 10.1172/JCI118128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nielsen S., Smith B. L., Christensen E. I., Knepper M. A., Agre P. CHIP28 water channels are localized in constitutively water-permeable segments of the nephron. J Cell Biol. 1993 Jan;120(2):371–383. doi: 10.1083/jcb.120.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Noble A. R., Abu-Kishk R. A., D'Aloia M. A., Williams B. C., Lush D. J. Cyclic GMP-linked pathway for renin secretion. Kidney Int. 1994 Dec;46(6):1588–1590. doi: 10.1038/ki.1994.454. [DOI] [PubMed] [Google Scholar]
  34. Nonoguchi H., Knepper M. A., Manganiello V. C. Effects of atrial natriuretic factor on cyclic guanosine monophosphate and cyclic adenosine monophosphate accumulation in microdissected nephron segments from rats. J Clin Invest. 1987 Feb;79(2):500–507. doi: 10.1172/JCI112840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Owen R. A., Molon-Noblot S., Hubert M. F., Siegl P. K., Eydelloth R. S., Keenan K. P. Juxtaglomerular cell hypertrophy and hyperplasia induced in rhesus monkeys by angiotensin II receptor antagonists. Lab Invest. 1994 Oct;71(4):543–551. [PubMed] [Google Scholar]
  36. Reinhardt R. R., Chin E., Zhou J., Taira M., Murata T., Manganiello V. C., Bondy C. A. Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases. J Clin Invest. 1995 Apr;95(4):1528–1538. doi: 10.1172/JCI117825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schmidt H. H., Lohmann S. M., Walter U. The nitric oxide and cGMP signal transduction system: regulation and mechanism of action. Biochim Biophys Acta. 1993 Aug 18;1178(2):153–175. doi: 10.1016/0167-4889(93)90006-b. [DOI] [PubMed] [Google Scholar]
  38. Schricker K., Della Bruna R., Hamann M., Kurtz A. Endothelium derived relaxing factor is involved in the pressure control of renin gene expression in the kidney. Pflugers Arch. 1994 Oct;428(3-4):261–268. doi: 10.1007/BF00724505. [DOI] [PubMed] [Google Scholar]
  39. Schricker K., Hegyi I., Hamann M., Kaissling B., Kurtz A. Tonic stimulation of renin gene expression by nitric oxide is counteracted by tonic inhibition through angiotensin II. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8006–8010. doi: 10.1073/pnas.92.17.8006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schricker K., Kurtz A. Liberators of NO exert a dual effect on renin secretion from isolated mouse renal juxtaglomerular cells. Am J Physiol. 1993 Aug;265(2 Pt 2):F180–F186. doi: 10.1152/ajprenal.1993.265.2.F180. [DOI] [PubMed] [Google Scholar]
  41. Schricker K., Ritthaler T., Krämer B. K., Kurtz A. Effect of endothelium-derived relaxing factor on renin secretion from isolated mouse renal juxtaglomerular cells. Acta Physiol Scand. 1993 Nov;149(3):347–354. doi: 10.1111/j.1748-1716.1993.tb09630.x. [DOI] [PubMed] [Google Scholar]
  42. Sigmon D. H., Fray J. C. Chemiosmotic control of renin release from isolated renin granules of rat kidneys. J Physiol. 1991 May;436:237–256. doi: 10.1113/jphysiol.1991.sp018548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tada M., Fukamizu A., Seo M. S., Takahashi S., Murakami K. Nucleotide sequence of rat renin cDNA. Nucleic Acids Res. 1988 Apr 25;16(8):3576–3576. doi: 10.1093/nar/16.8.3576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Takahashi N., Kondo Y., Ito O., Igarashi Y., Omata K., Abe K. Vasopressin stimulates Cl- transport in ascending thin limb of Henle's loop in hamster. J Clin Invest. 1995 Apr;95(4):1623–1627. doi: 10.1172/JCI117836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Terada Y., Moriyama T., Martin B. M., Knepper M. A., Garcia-Perez A. RT-PCR microlocalization of mRNA for guanylyl cyclase-coupled ANF receptor in rat kidney. Am J Physiol. 1991 Dec;261(6 Pt 2):F1080–F1087. doi: 10.1152/ajprenal.1991.261.6.F1080. [DOI] [PubMed] [Google Scholar]
  46. Terada Y., Tomita K., Nonoguchi H., Marumo F. Polymerase chain reaction localization of constitutive nitric oxide synthase and soluble guanylate cyclase messenger RNAs in microdissected rat nephron segments. J Clin Invest. 1992 Aug;90(2):659–665. doi: 10.1172/JCI115908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Uchida S., Sasaki S., Furukawa T., Hiraoka M., Imai T., Hirata Y., Marumo F. Molecular cloning of a chloride channel that is regulated by dehydration and expressed predominantly in kidney medulla. J Biol Chem. 1993 Feb 25;268(6):3821–3824. [PubMed] [Google Scholar]
  48. Uchida S., Sasaki S., Nitta K., Uchida K., Horita S., Nihei H., Marumo F. Localization and functional characterization of rat kidney-specific chloride channel, ClC-K1. J Clin Invest. 1995 Jan;95(1):104–113. doi: 10.1172/JCI117626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wada A., Tsutamoto T., Matsuda Y., Kinoshita M. Cardiorenal and neurohumoral effects of endogenous atrial natriuretic peptide in dogs with severe congestive heart failure using a specific antagonist for guanylate cyclase-coupled receptors. Circulation. 1994 May;89(5):2232–2240. doi: 10.1161/01.cir.89.5.2232. [DOI] [PubMed] [Google Scholar]
  50. Wilcox C. S., Welch W. J., Murad F., Gross S. S., Taylor G., Levi R., Schmidt H. H. Nitric oxide synthase in macula densa regulates glomerular capillary pressure. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11993–11997. doi: 10.1073/pnas.89.24.11993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES