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Am J Physiol Renal Physiol 275: F191-F197, 1998;
0363-6127/98 $5.00
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Vol. 275, Issue 2, F191-F197, August 1998

Natriuretic and kaliuretic activities of guanylin and uroguanylin in the isolated perfused rat kidney

Manasses C. Fonteles1, Richard N. Greenberg2, Helena S. A. Monteiro1, Mark G. Currie3, and Leonard R. Forte4

1 Clinical Research Unit, Federal University of Ceara and Ceara State University, 60434 Fortaleza, Brazil; 2 Department of Medicine, University of Kentucky and Lexington Veterans Affairs Medical Center, Lexington, Kentucky 40536; 3 Searle Research and Development, Monsanto, St. Louis 63167; and 4 Department of Pharmacology, School of Medicine, Missouri University and Truman Veterans Affairs Medical Center, Columbia, Missouri 65212

Guanylin and uroguanylin are novel peptides that activate membrane guanylate cyclases found in the kidney and intestine. We compared the effects of these peptides in the isolated perfused rat kidney. Both peptides are natriuretic and kaliuretic in this preparation. Uroguanylin (0.19-1.9 µM) increased glomerular filtration rate from 0.77 ± 0.07 to 1.34 ± 0.3 ml · g-1 · min-1 at the highest concentration. A maximal increase in Na+ excretion was achieved at 0.66 µM uroguanylin, with a reduction in fractional Na+ reabsorption from 78.7 ± 1.7 to 58.8 ± 4.4%. The highest dose of uroguanylin increased kaliuresis by 50%. Osmolar clearance doubled at the highest concentration of uroguanylin tested (P < 0.05). Guanylin also elicited a natriuresis and kaliuresis but appeared to be less potent than uroguanylin. The highest concentration of guanylin (1.3 µM) decreased fractional Na+ reabsorption from 73.9 ± 2.4 to 64.5 ± 4.0%, but lower doses were ineffective. Guanylin stimulated urine K+ excretion at the lowest concentration tested (0.33 µM) without any effect on Na+ excretion. These peptides may influence salt and water homeostasis by biological effects in the kidney that are mediated by the intracellular second messenger, cGMP.

glomerular filtration; sodium and potassium transport


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