Natriuretic and kaliuretic activities of guanylin and uroguanylin
in the isolated perfused rat kidney.
Fonteles, Manasses C., Richard N. Greenberg, Helena S. A. Monteiro,
Mark G. Currie, and Leonard R. Forte.
Clinical Research Unit of the Federal University of Ceara and Ceara
State University, Fortaleza, Brazil, Department of Medicine,
University of Kentucky and the Lexington VA Medical Center,
Lexington, KY 40536, Searle R&D, Monsanto Company, St. Louis MO
63167, and Department of Pharmacology, School of Medicine, Missouri
University and Truman VA Medical Center, Columbia, MO 65212.
APStracts 5:0072F, 1998.
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 to 1.9 [mu]M) increased GFR from 0.77+/-0.07 to
1.34+/-0.3 ml/g/min at the highest concentration. A maximal increase
in Na+ excretion was achieved at 0.66 [mu]M uroguanylin with a
reduction in fractional Na+ reabsorption from 78.7+/-1.7 % to 58.8+/
-4.4 %. The highest dose of uroguanylin increased kaliureseis by 50%.
Osmolar clearance doubled at the highest concentration of uroguanylin
tested (p<.05). Guanylin also elicited a natriuresis and
kaliuresis, but appeared to be less potent than uroguanylin. The
highest concentration of guanylin (1.3 [mu]M) 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 [mu]M) 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.
Received 13 December 1996; accepted in final form 18 March 1998.
APS Manuscript Number F348-6.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 6 April 1998