CHARACTERIZATION OF NOVEL PEPTOID AGONISTS FOR THE CCK-A RECEPTOR

The successful design of peptoid CCK-B receptor antagonists using rati onal approaches suggested that it might be feasible to develop similar non-peptide small molecule agonists with potential therapeutic applic ations, We now report the characterization of such a compound with ful l agonist activity at CCK-A receptors. on rat exocrine pancreatic acin ar cells. The compound, PD149164, stimulated a similar maximal respons e to CCK8 from the exocrine pancreas in anaesthetized rats in vivo, an d from isolated pancreatic acini in vitro it also generated intracellu lar Ca2+ oscillations similar to those evoked by CCK8. These effects w ere inhibited by the CCK-A antagonist L-364,718. Interestingly, the en antiomer of PD149164, PD151932, was a CCK-A antagonist and blocked PD1 49164 stimulated effects on the exocrine pancreas. The data indicate t hat it is possible to develop both agonist and antagonist activities i n enantiomers of small non-peptide molecules.