A novel effect of rebamipide: generation of [Ca(2+)](i) oscillations through activation of CCK(1) receptors in rat pancreatic acinar cells.
The protective effect of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]-propionic acid (rebamipide) on gastric mucosa is well established. Here we demonstrate that rebamipide acts on pancreatic acinar cells to generate oscillations of intracellular Ca(2+) concentration ([Ca(2+)](i)) through the activation of cholecystokinin subtype 1 (CCK(1)) receptors. At concentrations higher than 5 microM, rebamipide induced [Ca(2+)](i) oscillations in individual fura-2-loaded pancreatic acinar cells. The frequency of oscillations increased with increasing concentrations of rebamipide, while the latency between stimulation of cells and initiation of [Ca(2+)](i) oscillations decreased with increasing concentration. The [Ca(2+)](i) oscillations evoked by rebamipide were inhibited by the CCK(1) receptor antagonist L-364,718 but not by atropine or the CCK(2) receptor antagonist L-365,260 indicating that rebamipide is a nonpeptide CCK(1) receptor agonist.
Moon
S J
SJ
Department of Oral Biology, Yonsei University College of Dentistry, 134 Sinchon-dong, Seodaemun-gu, Seoul, South Korea.
Ahn
W
W
Lee
M G
MG
Kim
H
H
Lee
S I
SI
Seo
J T
JT
Case
R M
RM
Kim
K H
KH
D000409:Alanine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020109:Devazepide / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000494:pharmacology; D015363:Quinolones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D001570:Benzodiazepinones; D005456:Fluorescent Dyes; D018727:Muscarinic Antagonists; D010671:Phenylurea Compounds; D015363:Quinolones; D011949:Receptors, Cholecystokinin; C058121:L 365260; D001285:Atropine; D020109:Devazepide; C052785:rebamipide; D000409:Alanine; D002118:Calcium; D016257:Fura-2