Structure and activity of uroguanylin and guanylin from the
intestine and urine of rats.
Fan, Xiaohui, F. Kent Hamra, Roslyn M. London, Sammy L. Eber, William
J. Krause, Ronald H. Freeman, Christine E. Smith, Mark G. Currie, and
Leonard R. Forte.
The Truman VA Medical Center and Departments of Pharmacology,
Pathology and Anatomical Sciences, and Physiology, School of
Medicine, Columbia, MO 65212 and Searle Research and Development, St.
Louis, MO 63167
APStracts 4:0175E, 1997.
Uroguanylin and guanylin are related peptides that activate common
guanylate cyclase signaling molecules in the intestine and kidney.
Uroguanylin was isolated from urine and duodenum, but was not
detected in extracts from the colon of rats. Guanylin was identified
in extracts from small and large intestine, whereas guanylin was not
detected in urine. Uroguanylin and guanylin have distinct biochemical
and chromatographic properties that facilitated the separation,
purification and identification of these peptides. Northern assays
revealed that mRNA transcripts for uroguanylin were most abundant in
small intestine compared to large intestine, while guanylin mRNA
levels were greatest in large intestine relative to small intestine.
Synthetic rat uroguanylin and guanylin had similar potencies in the
activation of receptors in T84 intestinal cells. Production of
uroguanylin and guanylin in the mucosa of duodenum is consistent with
the postulate that both peptides influence the activity of an
intracellular cGMP signaling pathway that regulates the
transepithelial secretion of chloride and bicarbonate in the
intestinal epithelium.
Received 14 March 1997; accepted in final form 30 July 1997.
APS Manuscript Number E109-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997