The systematic isolation of circulating regulatory peptides which gene
rate cGMP as second messenger resulted in the identification of a nove
l member of the guanylin family. In the present study we describe the
purification and amino acid sequence of a new guanylate cyclase C acti
vating peptide (GCAP-II), GCAP-II contains 24 amino acids in the follo
wing sequence: FKTLRTIANDDCELCVACTGCL. Its molecular mass is 2597.7 Da
, The 16 C-terminal amino acids are identical to uroguanylin from huma
n urine, Native and synthetic GCAP-II activate GC-C, the specific guan
ylate cyclase receptor, of cultured human colon carcinoma (T84) cells,
GCAP-II stimulates chloride secretion in isolated human intestinal mu
cosa mediated by intracellular cGMP increase, GCAP-II specific antibod
ies were used to localize the peptide by immunohistochemistry in enter
o-endocrine cells of the colonic mucosa.