AJP - Renal Physiology, Vol 270, Issue 2 283-F288, Copyright © 1996 by American Physiological Society

ARTICLES

Extracellular cGMP inhibits transepithelial sodium transport by LLC-PK1 renal tubular cells

R. L. Chevalier, G. D. Fang and M. Garmey
Department of Pediatrics, University of Virginia, Charlottesville 22908, USA.

Both atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP) inhibit tubular sodium reabsorption by generation of guanosine 3',5'-cyclic monophosphate (cGMP). To determine the role of extracellular cGMP in this response, monolayers of porcine renal tubular LLC-PK1 cells were incubated for 5 min with ANP, SNP, cGMP, or 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) (10 nM to 0.1 mM). Transepithelial sodium transport was measured as amiloride-inhibitable short-circuit current (Isc). Incubation of cell monolayers with 1 microM of ANP, cGMP, or 8-BrcGMP inhibited Isc by > 70%, as did SNP at 100 microM (P < 0.01). Adenosine 3',5'-cyclic monophosphate (0.1 mM) had no significant effect. Incubation of monolayers with 1 microM LY-83583 (an inhibitor of guanylyl cyclase), 10 microM probenecid (an organic anion transport inhibitor), or preincubation with 1 microgram/ml nocodazole (a microtubule disrupter) reduced extracellular accumulation of cGMP (P < 0.05) and abolished the SNP-mediated reduction of Isc. However, addition of these inhibitors did not affect reduction of Isc by exogenous cGMP. We conclude that SNP inhibits sodium transport by LLC-PK1 monolayers through generation of cGMP but that extrusion of cGMP out the cell is necessary for its effect.

This article has been cited by other articles:

				F. Ahmed, B. A. Kemp, N. L. Howell, H. M. Siragy, and R. M. Carey Extracellular Renal Guanosine Cyclic 3'5'-Monophosphate Modulates Nitric Oxide and Pressure-Induced Natriuresis Hypertension, November 1, 2007; 50(5): 958 - 963. [Abstract] [Full Text] [PDF]

				R. A. M. H. Van Aubel, P. H. E. Smeets, J. J. M. W. van den Heuvel, and F. G. M. Russel Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites Am J Physiol Renal Physiol, February 1, 2005; 288(2): F327 - F333. [Abstract] [Full Text] [PDF]

				R. A. M. H. van Aubel, P. H. E. Smeets, J. G. P. Peters, R. J. M. Bindels, and F. G. M. Russel The MRP4/ABCC4 Gene Encodes a Novel Apical Organic Anion Transporter in Human Kidney Proximal Tubules: Putative Efflux Pump for Urinary cAMP and cGMP J. Am. Soc. Nephrol., March 1, 2002; 13(3): 595 - 603. [Abstract] [Full Text] [PDF]

				S. F. HAMM-ALVAREZ and M. P. SHEETZ Microtubule-Dependent Vesicle Transport: Modulation of Channel and Transporter Activity in Liver and Kidney Physiol Rev, October 1, 1998; 78(4): 1109 - 1129. [Abstract] [Full Text] [PDF]

				X.-H. Jin, Z.-Q. Wang, H. M. Siragy, R. L. Guerrant, and R. M. Carey Regulation of jejunal sodium and water absorption by angiotensin subtype receptors Am J Physiol Regulatory Integrative Comp Physiol, August 1, 1998; 275(2): R515 - R523. [Abstract] [Full Text] [PDF]

				J. N. Bech, C. B. Nielsen, P. Ivarsen, K. T. Jensen, and E. B. Pedersen Dietary sodium affects systemic and renal hemodynamic response to NO inhibition in healthy humans Am J Physiol Renal Physiol, May 1, 1998; 274(5): F914 - F923. [Abstract] [Full Text] [PDF]

				E. Eitle, S. Hiranyachattada, H. Wang, and P. J. Harris Inhibition of proximal tubular fluid absorption by nitric oxide and atrial natriuretic peptide in rat kidney Am J Physiol Cell Physiol, April 1, 1998; 274(4): C1075 - C1080. [Abstract] [Full Text] [PDF]