BIBP3226 (N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-D-
arginine amide) has been used to examine the presence of
neuropeptide Y Y1 receptors in 3 gastrointestinal epithelial preparations, namely the rat jejunum and descending colon mucosae and a human colonic
adenocarcinoma cell line. The selective Y1 receptor antagonist (1 microM
BIBP3226) had no significant effect upon either
peptide YY (PYY) responses or on electric field stimulated changes in electrogenic ion transport in rat jejunum mucosa. Partial inhibition of PYY responses was observed following
BIBP3226 pretreatment of rat colon mucosal preparations in the presence and absence of
tetrodotoxin. Responses to the Y1 selective agonist [Leu31,Pro34]
neuropeptide Y ([Leu31, Pro34]NPY) in descending colon preparations were significantly attenuated by
BIBP3226 (1 microM). The same concentration of antagonist abolished responses to PYY and [Leu31,Pro34]NPY but had no effect upon human
pancreatic polypeptide (
hPP) in monolayer cultures of the human
adenocarcinoma cell line, Colony-6. Schild analysis of
BIBP3226 antagonism of PYY responses in Colony-6 cells provided a pA2 value of 7.9 with a Hill slope of 1.03, indicating competitive antagonism at these epithelial Y1 receptors.