This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Potthast, R. Articles by Kuhn, M. Search for Related Content PubMed PubMed Citation Articles by Potthast, R. Articles by Kuhn, M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Dietary Sodium Hazardous Substances DB SODIUM CHLORIDE

High Salt Intake Increases Uroguanylin Expression in Mouse Kidney¹

Institute of Pharmacology and Toxicology (R.P., M.K.) and Department of Internal Medicine, Experimental Nephrology, Westfaelische Wilhelms-Universitaet Muenster, Muenster 48129, Germany; Institute of Cell Biology (E.E.), ETH Hoenggerberg, Zuerich 8093, Switzerland; and Division of Pediatric Endocrinology (L.A.S.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2579

Address all correspondence and requests for reprints to: Dr. Michaela Kuhn, Department of Pharmacology and Toxicology, Westfaelische Wilhelms-Universitaet Muenster, Domagkstrasse 12, D-48129 Muenster, Germany. E-mail: mkuhn{at}uni-muenster.de

The intestinal peptides, guanylin and uroguanylin, may have an important role in the endocrine control of renal function. Both peptides and their receptor, guanylyl cyclase C (GC-C), are also expressed within the kidney, suggesting that they may act locally in an autocrine/paracrine fashion. However, their physiological regulation within the kidney has not been studied. To begin to address this issue, we evaluated the distribution of uroguanylin and guanylin messenger RNA (mRNA) in the mouse nephron and the regulation of renal expression by changes in dietary salt/water intake. Expression was determined in 1) wild-type mice, 2) two strains of receptor-guanylyl cyclase-deficient mice (ANP-receptor-deficient, GC-A-/-, and GC-C-deficient mice); and 3) cultured renal epithelial (M-1) cells, by RT-PCR, Northern blotting and immunocytochemistry.

Renal uroguanylin messenger RNA expression was higher than guanylin and had a different distribution pattern, with highest levels in the proximal tubules, whereas guanylin was mainly expressed in the collecting ducts. Uroguanylin expression was significantly lower in GC-C-/- mice than in GC-A-/- and wild-types, suggesting that absence of a receptor was able to down-regulate ligand expression. Salt-loading (1% NaCl in drinking water) increased uroguanylin-mRNA expression by >1.8-fold but had no effect on guanylin expression. Uroguanylin but not guanylin transcripts were detected in M-1 cells and increased in response to hypertonic media (+NaCl or mannitol). Our results indicate that high-salt intake increases uroguanylin but not guanylin expression in the mouse kidney. The synthesis of these peptides by tubular epithelium may contribute to the local control of renal function and its adaptation to dietary salt.

This article has been cited by other articles:

				A. Kilic, A. Bubikat, B. Gassner, H. A. Baba, and M. Kuhn Local Actions of Atrial Natriuretic Peptide Counteract Angiotensin II Stimulated Cardiac Remodeling Endocrinology, September 1, 2007; 148(9): 4162 - 4169. [Abstract] [Full Text] [PDF]

				T. Berndt, L. F. Thomas, T. A. Craig, S. Sommer, X. Li, E. J. Bergstralh, and R. Kumar Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption PNAS, June 26, 2007; 104(26): 11085 - 11090. [Abstract] [Full Text] [PDF]

				A. Sindic and E. Schlatter Mechanisms of action of uroguanylin and guanylin and their role in salt handling Nephrol. Dial. Transplant., November 1, 2006; 21(11): 3007 - 3012. [Full Text] [PDF]

				A. Sindic and E. Schlatter Cellular Effects of Guanylin and Uroguanylin J. Am. Soc. Nephrol., March 1, 2006; 17(3): 607 - 616. [Abstract] [Full Text] [PDF]

				W. R Thelin, C. A Hodson, and S. L Milgram Beyond the brush border: NHERF4 blazes new NHERF turf J. Physiol., August 15, 2005; 567(1): 13 - 19. [Abstract] [Full Text] [PDF]

				M. Kikuchi, S. Fujimoto, H. Fukae, H. Kinoshita, T. Kita, M. Nakazato, and T. Eto Role of Uroguanylin, a Peptide with Natriuretic Activity, in Rats with Experimental Nephrotic Syndrome J. Am. Soc. Nephrol., February 1, 2005; 16(2): 392 - 397. [Abstract] [Full Text] [PDF]

				M. Kuhn, M. Voss, D. Mitko, J. Stypmann, C. Schmid, N. Kawaguchi, F. Grabellus, and H. A. Baba Left ventricular assist device support reverses altered cardiac expression and function of natriuretic peptides and receptors in end-stage heart failure Cardiovasc Res, November 1, 2004; 64(2): 308 - 314. [Abstract] [Full Text] [PDF]

				S. Yuge, K. Inoue, S. Hyodo, and Y. Takei A Novel Guanylin Family (Guanylin, Uroguanylin, and Renoguanylin) in Eels: POSSIBLE OSMOREGULATORY HORMONES IN INTESTINE AND KIDNEY J. Biol. Chem., June 13, 2003; 278(25): 22726 - 22733. [Abstract] [Full Text] [PDF]

				V. Thongboonkerd, J. B. Klein, W. M. Pierce, A. W. Jevans, and J. M. Arthur Sodium loading changes urinary protein excretion: a proteomic analysis Am J Physiol Renal Physiol, June 1, 2003; 284(6): F1155 - F1163. [Abstract] [Full Text] [PDF]

				K. A. Steinbrecher, J. A. Rudolph, G. Luo, and M. B. Cohen Coordinate upregulation of guanylin and uroguanylin expression by hypertonicity in HT29-18-N2 cells Am J Physiol Cell Physiol, December 1, 2002; 283(6): C1729 - C1737. [Abstract] [Full Text] [PDF]

				R. Holtwick, M. Gotthardt, B. Skryabin, M. Steinmetz, R. Potthast, B. Zetsche, R. E. Hammer, J. Herz, and M. Kuhn Smooth muscle-selective deletion of guanylyl cyclase-A prevents the acute but not chronic effects of ANP on blood pressure PNAS, May 14, 2002; 99(10): 7142 - 7147. [Abstract] [Full Text] [PDF]

				A. Sindice, C. Basoglu, A. Cerci, J. R. Hirsch, R. Potthast, M. Kuhn, Y. Ghanekar, S. S. Visweswariah, and E. Schlatter Guanylin, Uroguanylin, and Heat-stable Euterotoxin Activate Guanylate Cyclase C and/or a Pertussis Toxin-sensitive G Protein in Human Proximal Tubule Cells J. Biol. Chem., May 10, 2002; 277(20): 17758 - 17764. [Abstract] [Full Text] [PDF]

				M. Pierkes, S. Gambaryan, P. Boknik, S. M. Lohmann, W. Schmitz, R. Potthast, R. Holtwick, and M. Kuhn Increased effects of C-type natriuretic peptide on cardiac ventricular contractility and relaxation in guanylyl cyclase A-deficient mice Cardiovasc Res, March 1, 2002; 53(4): 852 - 861. [Abstract] [Full Text] [PDF]