A novel effect of rebamipide: Generation of [Ca²⁺](i) oscillations through activation of CCK₁ 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 Ca²⁺ concentration ([Ca²⁺](i)) through the activation of cholecystokinin subtype 1 (CCK₁) receptors. At concentrations higher than 5 μM, rebamipide induced [Ca²⁺](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 [Ca²⁺](i) oscillations decreased with increasing concentration. The [Ca²⁺](i) oscillations evoked by rebamipide were inhibited by the CCK₁ receptor antagonist L-364,718 but not by atropine or the CCK₂ receptor antagonist L-365,260 indicating that rebamipide is a nonpeptide CCK₁ receptor agonist. Copyright (C) 2000 Elsevier Science B.V.