CHARACTERIZATION OF HUMAN UROGUANYLIN - A MEMBER OF THE GUANYLIN PEPTIDE FAMILY

Guanylin, a peptide homelogue of the bacterial heat-stable enterotoxin s (ST), is an endogenous activator of guanylate cyclase C (GC-C). We h ave initiated a search for other members of the guanylin peptide famil y and in the current study describe a ''guanylin-like peptide'' from h uman urine. Bioactivity was monitored by determining the effect of uri ne extracts on T84 cell guanosine 3',5'-cyclic monophosphate (cGMP) le vels. Purification yielded two bioactive peaks of peptides that, when sequenced by NH2-terminal analysis, possessed 15 and 16 amino acids. T he sequence of the smaller peptide represented an NH2-terminal truncat ion of the larger peptide. We have termed the larger peptide human uro guanylin; it has the following amino acid sequence: NDDCELCVNVACTGCL. Human uroguanylin shares amino acid sequence homology with guanylin an d ST. Synthetic uroguanylin increased cGMP levels in T84 cells, compet ed with I-125-labeled ST for receptors, and stimulated Cl- secretion a s reflected by an increased short-circuit current. Thus we report the isolation from human urine of a unique peptide, uroguanylin, that beha ves in a manner similar to guanylin and appears to be a new member of this peptide family.