Characterization of human uroguanylin: A member of the guanylin peptide family

Toshihiro Kita, Christine E. Smith, Kam F. Fok, Kevin L. Duffin, William M. Moore, Peter J. Karabatsos, James F. Kachur, F. Kent Hamra, Nykolai V. Pidhorodeckyj, Leonard R. Forte, Mark G. Currie

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Abstract

Guanylin, a peptide homologue of the bacterial heat-stable enterotoxins (ST), is an endogenous activator of guanylate cyclase C (GC-C). We have initiated a search for other members of the guanylin peptide family and in the current study describe a 'guanylin-like peptide' from human urine. Bioactivity was monitored by determining the effect of urine extracts on T84 cell guanosine 3',5'-cyclic monophosphate (cGMP) levels. Purification yielded two bioactive peaks of peptides that, when sequenced by NH2-terminal analysis, possessed 15 and 16 amino acids. The sequence of the smaller peptide represented an NH2-terminal truncation of the larger peptide. We have termed the larger peptide human uroguanylin; it has the following amino acid sequence: NDDCELCVNVACTGCL. Human uroguanylin shares amino acid sequence homology with guanylin and ST. Synthetic uroguanylin increased cGMP levels in T84 cells, competed with 125I-labeled ST for receptors, and stimulated Cl- secretion as reflected by an increased short-circuit current. Thus we report the isolation from human urine of a unique peptide, uroguanylin, that behaves in a manner similar to guanylin and appears to be a new member of this peptide family.

Original languageEnglish (US)
Pages (from-to)F342-F348
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume266
Issue number2 35-2
StatePublished - Jan 1 1994

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Keywords

  • T84 cell
  • chloride secretion
  • guanosine 3',5'-cyclic monophosphate
  • guanylate cyclase
  • rat colon

ASJC Scopus subject areas

  • Physiology

Cite this

Kita, T., Smith, C. E., Fok, K. F., Duffin, K. L., Moore, W. M., Karabatsos, P. J., Kachur, J. F., Hamra, F. K., Pidhorodeckyj, N. V., Forte, L. R., & Currie, M. G. (1994). Characterization of human uroguanylin: A member of the guanylin peptide family. American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 266(2 35-2), F342-F348.