Effects of cholecystokinin-receptor antagonists on Fos-like immunoreactivity stimulated by sulfated cholecystokinin-8 in neurons of the myenteric plexus and hindbrain of rats.

Academic Article

Abstract

  • OBJECTIVE: To evaluate the role of cholecystokinin (CCK)-receptor antagonists in the activation of enteric and hindbrain neurons by sulfated CCK-8. ANIMALS: 81 male Sprague-Dawley rats. PROCEDURE: Rats were allocated to 10 groups (5 to 22 rats/group). Each rat received 2 IP injections (15 minutes between injections). The first injection consisted of a specific CCK2-receptor (CCK2R) antagonist (L365,260; 150, 500, or 1,000 microg/kg), a specific CCK1-receptor (CCK1R) antagonist (devazepide; 150 microg/kg), or 1% dimethyl sulfoxide (DMSO [ie, vehicle]), and the second injection consisted of sulfated CCK-8 (10 microg/kg) or saline (0.9% NaCl) solution. Rats were anesthetized and perfused with 500 mL of Krebs saline solution, and the myenteric plexuses of the duodenum and jejunum were collected. Rats were then perfused with 500 mL of phosphate-buffered 4% formaldehyde solution; rats were then euthanatized, and the hindbrain of each was harvested. Tissues were stained by use of a diaminobenzidine reaction enhanced with nickel to reveal Fos-like immunoreactivity (Fos-LI), a marker of neuronal activation, in the aforementioned neurons. RESULTS: Sulfated CCK-8 significantly increased Fos-LI in the myenteric and hindbrain neurons, compared with values for the DMSO injections. All dosages of L365,260 failed to attenuate this increase; however, injection of devazepide attenuated the increase in Fos-LI. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the results of this study reveals that sulfated CCK-8 activates myenteric and hindbrain neurons of rats primarily through CCK1 R. It provides evidence that CCK2R are lacking or not functional in the gastrointestinal tract of rats.
  • Authors

    Keywords

  • Animals, Gene Expression, Male, Myenteric Plexus, Neurons, Proto-Oncogene Proteins c-fos, Rats, Rats, Sprague-Dawley, Receptors, Cholecystokinin, Rhombencephalon, Sincalide
  • Digital Object Identifier (doi)

    Author List

  • Webb T; Gulley S; Esdaile AR; Pruitt F; Sharma SK; Williams CS; Sayegh AI
  • Start Page

  • 1308
  • End Page

  • 1313
  • Volume

  • 66
  • Issue

  • 8