Selective inhibition of neuropeptide Y Y1 receptors by BIBP3226 in rat and human epithelial preparations.

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.