AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 4 708-G716, Copyright © 1996 by American Physiological Society

ARTICLES

Opossum colonic mucosa contains uroguanylin and guanylin peptides

F. K. Hamra, W. J. Krause, S. L. Eber, R. H. Freeman, C. E. Smith, M. G. Currie and L. R. Forte
Truman Veterans Affairs Medical Center, Columbia, Missouri, USA. pharmfkh@muccmail.missouri.edu

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 approximately 3.0, eluted from C18 reverse-phase high-performance liquid chromatography (RP-HPLC) columns at 8-9% acetonitrile, elicited greater guanosine 3', 5'-cyclic monophosphate (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 approximately 6.0, eluted at 15-16% acetonitrile on C18 RP-HPLC columns, 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 Try-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.

This article has been cited by other articles:

				L. D'Este, H. Kulaksiz, U. Rausch, R. Vaccaro, T. Wenger, Y. Tokunaga, T. G. Renda, and Y. Cetin Expression of guanylin in "pars tuberalis-specific cells" and gonadotrophs of rat adenohypophysis PNAS, February 1, 2000; 97(3): 1131 - 1136. [Abstract] [Full Text] [PDF]

				S. L. Carrithers, S. L. Eber, L. R. Forte, and R. N. Greenberg Increased urinary excretion of uroguanylin in patients with congestive heart failure Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H538 - H547. [Abstract] [Full Text] [PDF]

				L. R. Forte, R. M. London, R. H. Freeman, and W. J. Krause Guanylin peptides: renal actions mediated by cyclic GMP Am J Physiol Renal Physiol, February 1, 2000; 278(2): F180 - F191. [Abstract] [Full Text] [PDF]

				M. C. Fonteles, R. N. Greenberg, H. S. A. Monteiro, M. G. Currie, and L. R. Forte Natriuretic and kaliuretic activities of guanylin and uroguanylin in the isolated perfused rat kidney Am J Physiol Renal Physiol, August 1, 1998; 275(2): F191 - F197. [Abstract] [Full Text] [PDF]

				X. Fan, F. K. Hamra, R. M. London, S. L. Eber, W. J. Krause, R. H. Freeman, C. E. Smith, M. G. Currie, and L. R. Forte Structure and activity of uroguanylin and guanylin from the intestine and urine of rats Am J Physiol Endocrinol Metab, November 1, 1997; 273(5): E957 - E964. [Abstract] [Full Text] [PDF]

				F. K. Hamra, S. L. Eber, D. T. Chin, M. G. Currie, and L. R. Forte Regulation of intestinal uroguanylin/guanylin receptor-mediated responses by mucosal acidity PNAS, March 18, 1997; 94(6): 2705 - 2710. [Abstract] [Full Text] [PDF]