Pharmacological characterization of rebamipide: its cholecystokinin CCK1 receptor binding profile and effects on Ca2+ mobilization and amylase release in rat pancreatic acinar cells.
We previously reported that rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]-propionic acid) generated oscillations of intracellular Ca2+ concentration ([Ca2+]i) probably through the activation of cholecystokinin type 1 (CCK1) 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 IC50 values of 3.13 nM and 37.7 microM, respectively. CCK-8S usually evoked [Ca2+]i oscillations at concentrations lower than 50 pM, and it induced biphasic [Ca2+]i increases at higher concentrations. In contrast to CCK-8S, rebamipide only induced [Ca2+]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 [Ca2+]i, suggesting that rebamipide might be a partial agonist at cholecystokinin CCK1 receptors. Although rebamipide induced [Ca2+]i oscillations by activating the cholecystokinin CCK1 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 Ca2+ -mobilizing action, and it is also an antagonist for the amylase-releasing action of CCK.
Moon
Seok Jun
SJ
Department of Oral Biology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Dentistry, Seoul 120-752, Republic of Korea.
An
Jeong Mi
JM
Kim
Juyeon
J
Lee
Syng-Ill
SI
Ahn
Wooin
W
Kim
Kyung Hwan
KH
Seo
Jeong Taeg
JT
D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007457:Iodine Radioisotopes; D007700:Kinetics; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015363:Quinolones / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D043886:Receptor, Cholecystokinin A / Q000819:agonists / Q000378:metabolism*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013388:Succinimides / Q000378:metabolism
C090019:8-sulfocholecystokinin octapeptide; D000975:Antioxidants; C044758:Bolton Hunter-cholecystokinin octapeptide; D007457:Iodine Radioisotopes; D015363:Quinolones; D043886:Receptor, Cholecystokinin A; D013388:Succinimides; D002766:Cholecystokinin; D000681:Amylases; C052785:rebamipide; D012844:Sincalide; D000409:Alanine; D002118:Calcium