Pharmacological characterization of rebamipide: its cholecystokinin CCK1 receptor binding profile and effects on Ca2+ mobilization and amylase release in rat pancreatic acinar cells.
Pharmacological characterization of rebamipide: its cholecystokinin CCK1 receptor binding profile and effects on Ca2+ mobilization and amylase release in rat pancreatic acinar cells.
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DOI：
10.1016/j.ejphar.2004.10.032
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发表时间：
2004-11
影响因子：
5
通讯作者：
S. J. Moon;J. An;Juyeon Kim;Syng‐Ill Lee;W. Ahn;K. Kim;J. Seo
中科院分区：
文献类型：
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作者：
S. J. Moon;J. An;Juyeon Kim;Syng‐Ill Lee;W. Ahn;K. Kim;J. Seo
我们之前报道了利巴米胺（2-（4-氯苯甲酰胺）-3-[2(1H)-喹啉-4-基]-丙酸）可能通过激活大鼠胰腺腺泡细胞中的胆囊收缩素1型（CCK1）受体而产生细胞内Ca2+浓度（[Ca2+]i）的振荡。因此，在本研究中，我们旨在建立利巴米胺在大鼠胰腺腺泡细胞中的药理特性。CCK-8S和利巴米胺抑制[125I]BH-CCK-8S与大鼠胰腺腺泡细胞膜结合，ic50值分别为3.13 nM和37.7 μM。CCK-8S通常在浓度低于50 pM时引起[Ca2+]震荡，在较高浓度时引起双相[Ca2+]升高。与CCK-8S相比，我们在本研究中使用的所有浓度的利巴米胺仅诱导[Ca2+]振荡。此外，利巴米胺被证明可以抑制高浓度cck - 8s诱导的[Ca2+]i的双相升高，这表明利巴米胺可能是cck1受体胆囊收缩素的部分激动剂。虽然利巴米胺通过激活胆囊收缩素cck1受体诱导[Ca2+]振荡，但利巴米胺不引起淀粉酶释放，仅可逆且剂量依赖性地抑制cck刺激的淀粉酶释放。然而，利巴米胺不抑制氨基酚、血管活性肠多肽（VIP）和福斯克林诱导的淀粉酶释放。这些数据表明，利巴米胺作为Ca2+动员作用的部分激动剂，它也是CCK的淀粉酶释放作用的拮抗剂。
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 IC50values of 3.13 nM and 37.7 μM, respectively. CCK-8S usually evoked [Ca2+]ioscillations at concentrations lower than 50 pM, and it induced biphasic [Ca2+]iincreases at higher concentrations. In contrast to CCK-8S, rebamipide only induced [Ca2+]ioscillations 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 CCK1receptors. Although rebamipide induced [Ca2+]ioscillations by activating the cholecystokinin CCK1receptors, 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.