EVALUATION OF INTESTINAL ANTISECRETORY PEPTIDES COEFFICIENT OF DISSOCIATION - A FUNCTIONAL-APPROACH

The aim of this study was to determine the coefficient of dissociation (K-d) of three three intestinal antisecretory peptides, peptide YY (P YY), galanin (GAL), and somatostatin-28 (SRIF) by a functional approac h. The variations iii short-circuit current (Delta Isc) due to the mod ification of ionic transport across rat and rabbit small intestine wer e assessed in vitro, using Ussing chambers. Determination of K-d was m ade by mathematical analysis of concentration-response relationships. We found K-d values for GAL and SRIF of 1.6 and 3.67 nM, respectively, in rabbit ileum. In rat jejunum, we found K-d of 0.44 nM for PW and 1 .75 for SRIF. Our data are in close agreement with those derived from binding studies suggesting that evaluation of K-d by this functional a pproach can be used to assess the antisecretory potency of peptides or of analogs analogs whose receptors in intestine have not yet been cha racterized.