PD 135158, a CCKB/gastrin receptor antagonist, stimulates rat pancreatic enzyme secretion as a CCKA receptor agonist

Eur J Pharmacol. 1993 Sep 21;242(1):105-8. doi: 10.1016/0014-2999(93)90016-b.

Abstract

The CCKB/gastrin receptor antagonist, PD 135158 (CAM 1028), surprisingly stimulates lipase release from isolated rat pancreatic acini dose dependently in a biphasic manner, with identical efficacy but lower potency compared to cholecystokinin octapeptide (CCK-8). Half-maximal stimulation occurred at 0.6 microM and maximal secretion was induced at 50 microM. Supramaximal concentrations decreased lipase release. Acinar lipase secretion in response to 25 pM CCK-8 or 1 microM CAM-1028 was abolished by 5 microM of the specific CCKA receptor antagonist loxiglumide (CR 1505), half-maximal inhibition was observed at 0.6 microM for CCK-8 and 0.4 microM for PD 135158. These data demonstrate that the CCKB/gastrin receptor antagonist, PD 135158, acts as a full agonist at the rat pancreatic CCKA receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Cholecystokinin / antagonists & inhibitors
  • Drug Interactions
  • Indoles / pharmacology*
  • Lipase / metabolism
  • Meglumine / analogs & derivatives*
  • Meglumine / pharmacology
  • Pancreas / drug effects*
  • Pancreas / enzymology
  • Proglumide / analogs & derivatives
  • Proglumide / pharmacology
  • Rats
  • Sincalide / pharmacology

Substances

  • Anti-Anxiety Agents
  • Indoles
  • PD 135158
  • Meglumine
  • loxiglumide
  • Cholecystokinin
  • Lipase
  • Proglumide
  • Sincalide