We previously reported that rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)- quinolinon-4-yl]-propionic acid) generated oscillations of intracellular Ca 2+ concentration ([Ca 2+] i) probably through the activation of cholecystokinin type 1 (CCK 1) receptors in rat pancreatic acinar cells. Therefore, in the present study, we aimed to establish the pharmacological characteristics of rebamipide in rat pancreatic acinar cells. CCK-8S and rebamipide inhibited [ 125I]BH-CCK-8S binding to rat pancreatic acinar cell membranes with IC 50 values of 3.13 nM and 37.7 μM, respectively. CCK-8S usually evoked [Ca 2+] i oscillations at concentrations lower than 50 pM, and it induced biphasic [Ca 2+] i increases at higher concentrations. In contrast to CCK-8S, rebamipide only induced [Ca 2+] i oscillations at all the concentrations we used in this study. In addition, rebamipide was shown to inhibit high concentrations of CCK-8S-induced biphasic increases in [Ca 2+] i, suggesting that rebamipide might be a partial agonist at cholecystokinin CCK 1 receptors. Although rebamipide induced [Ca 2+] i oscillations by activating the cholecystokinin CCK 1 receptors, rebamipide did not cause amylase release and only inhibited CCK-stimulated amylase release reversibly and dose-dependently. However, rebamipide did not inhibit carbachol-, vasoactive intestinal polypeptide (VIP)-, and forskolin-induced amylase releases. These data indicate that rebamipide functions as a partial agonist for Ca 2+-mobilizing action, and it is also an antagonist for the amylase-releasing action of CCK.
Bibliographical noteFunding Information:
This work was supported by the Research Fund from Yonsei University for 2003.
All Science Journal Classification (ASJC) codes