Characterization of human uroguanylin: a member of the guanylin peptide family.
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.
Kita
T
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Monsanto Corporate Research, St. Louis, Missouri 63167.
Smith
C E
CE
Fok
K F
KF
Duffin
K L
KL
Moore
W M
WM
Karabatsos
P J
PJ
Kachur
J F
JF
Hamra
F K
FK
Pidhorodeckyj
N V
NV
Forte
L R
LR
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
D002712:Chlorides; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; C072685:guanylin; C084362:uroguanylin; D006152:Cyclic GMP