Colonic mucosa of the opossum contains uroguanylin and guanylin
peptides.
Hamra, F. Kent, William J. Krause, Sammy L. Eber, Ronald H. Freeman,
Christine E. Smith, Mark G. Currie, and Leonard R. Forte.
The Truman VA Medical Center and Departments of Pharmacology,
Anatomy, and Physiology, School of Medicine, Missouri University,
Columbia, MO 65212 and Searle Research and Development5, St. Louis,
MO 63167
APStracts 2:0214G, 1995.
Uroguanylin and guanylin are structurally related peptides that
activate an intestinal form of membrane guanylate cyclase (GC-C).
Guanylin was isolated from the intestine, but uroguanylin was
isolated from urine, thus a tissue source for uroguanylin was sought.
In these experiments, uroguanylin and guanylin were separated and
purified independently from colonic mucosa and urine of opossums.
Colonic, urinary and synthetic forms of uroguanylin had an
isoelectric point of 3.0, eluted from C18 RP-HPLC columns at 8-9%
acetonitrile, elicited greater cGMP responses in T84 cells at pH 5.5
than pH 8 and were not cleaved and inactivated by pretreatment with
chymotrypsin. In contrast, colonic, urinary and synthetic guanylin
had an isoelectric point of 6.0, eluted at 15-16% acetonitrile on C18
RP-HPLC, stimulated greater cGMP responses in T84 cells at pH 8 than
pH 5.5 and were inactivated by chymotrypsin, which hydrolyzed the
Phe-Ala or Tyr-Ala bonds within guanylin. Uroguanylin joins guanylin
as an intestinal peptide that may participate in an intrinsic pathway
for cGMP-mediated regulation of intestinal salt and water transport.
Moreover, uroguanylin and guanylin in urine may be derived from the
intestinal mucosa, thus implicating these peptides in an endocrine
mechanism linking the intestine with the kidney.
Received 22 May 1995; accepted in final form 9 October 1995.
APS Manuscript Number G223-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95