Evaluation of intestinal antisecretory peptides coefficient of dissociation: a functional approach.
The aim of this study was to determine the coefficient of dissociation (Kd) of three intestinal antisecretory peptides, peptide YY (PYY), galanin (GAL), and somatostatin-28 (SRIF) by a functional approach. The variations in short-circuit current (DeltaIsc) due to the modification of ionic transport across rat and rabbit small intestine were assessed in vitro, using Ussing chambers. Determination of Kd was made by mathematical analysis of concentration-response relationships. We found Kd values for GAL and SRIF of 1.6 and 3.67 nM, respectively, in rabbit ileum. In rat jejunum, we found Kd of 0.44 nM for PYY and 1.75 for SRIF. Our data are in close agreement with those derived from binding studies suggesting that evaluation of Kd by this functional approach can be used to assess the antisecretory potency of peptides or of analogs whose receptors in intestine have not yet been characterized.
Eto
B
B
Conservatoire National des Arts et Metiers, Laboratoire de Biologie, Paris, France.
D000818:Animals; D002712:Chlorides / Q000378:metabolism; D006224:Cricetinae; D019004:Galanin / Q000494:pharmacology*; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology*; D013552:Swine
D002712:Chlorides; D005768:Gastrointestinal Hormones; D010455:Peptides; D019894:Peptide YY; D013004:Somatostatin; D019004:Galanin