Uroguanylin: Structure and activity of a second endogenous peptide that stimulates intestinal guanylate cyclase

F. Kent Hamra, Leonard R. Forte, Sammy L. Eber, Nykolai V. Pidhorodeckyj, William J. Krause, Ronald H. Freeman, David T. Chin, Jay A. Tompkins, Kam F. Fok, Christine E. Smith, Kevin L. Duffin, Ned R. Siegel, Mark G. Currie

Research output: Contribution to journalArticle

296 Scopus citations

Abstract

The intestinal hormone guanylin and bacterial heat-stable enterotoxins (STs) are members of a peptide family that activates intestinal membrane guanylate cyclase. Two different peptides that activate the human intestinal T84 cell guanylate cyclase have been purified from urine and intestinal mucosa of opossums (Didelphis virginiana). The highly acidic peptide, QEDCELCINVACTGC, was named uroguanylin because it was isolated from urine and shares 53% identity with guanylin. A second peptide, SHTCEICAFAACAGC, was purified from urine and intestinal mucosa. This alanine-rich peptide was 47% identical to uroguanylin and 73% identical to human guanylin, suggesting that it may be an opossum homologue of guanylin. Synthetic uroguanylin-(2-15) (i.e., EDCELCINVACTGC) was 10-fold more potent than synthetic rat guanylin, but both peptides were less potent than Escherichia colt ST in the T84 cell cGMP bioassay. Uroguanylin-(2-15) and guanylin inhibited 125I-ST binding to T84 cell receptors in competitive radioligand binding assays. Transepithelial Cl- secretion was stimulated by 1 μM uroguanylin, indicated by an increase in the short circuit current of T84 cells. Thus, uroguanylin is another paracrine hormone in the emerging peptide family that activates intestinal membrane guanylate cyclase. The second peptide may be the opossum form of guanylin, or perhaps it is still another member of this peptide family. The presence of uroguanylin and guanylin in urine and receptors in proximal tubules suggests that these peptides may also originate from renal tissue and may regulate kidney function.

Original languageEnglish (US)
Pages (from-to)10464-10468
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number22
DOIs
StatePublished - Nov 15 1993

Keywords

  • Chloride secretion
  • Cyclic GMP
  • Guanylin
  • Urine

ASJC Scopus subject areas

  • General

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