title: Characterization of human uroguanylin: a member of the guanylin peptide family.
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.
authors.affiliation: Monsanto Corporate Research, St. Louis, Missouri 63167.
authors.forename: T
authors.initials: T
authors.lastname: Kita
authors.forename: C E
authors.initials: CE
authors.lastname: Smith
authors.forename: K F
authors.initials: KF
authors.lastname: Fok
authors.forename: K L
authors.initials: KL
authors.lastname: Duffin
authors.forename: W M
authors.initials: WM
authors.lastname: Moore
authors.forename: P J
authors.initials: PJ
authors.lastname: Karabatsos
authors.forename: J F
authors.initials: JF
authors.lastname: Kachur
authors.forename: F K
authors.initials: FK
authors.lastname: Hamra
authors.forename: N V
authors.initials: NV
authors.lastname: Pidhorodeckyj
authors.forename: L R
authors.initials: LR
authors.lastname: Forte
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D004926:Escherichia coli; D005768:Gastrointestinal Hormones; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides; D009893:Opossums; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000652:urine*; D011869:Radioligand Assay; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: D002712:Chlorides; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; C072685:guanylin; C084362:uroguanylin; D006152:Cyclic GMP