Deactivation of ROCK-II by Y-27632 enhances basolateral pancreatic enzyme secretion and acute pancreatitis induced by CCK analogues |
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Authors: | Kusama Kazushige Nozu Fumihiko Awai Toshinari Tanaka Shigeki Honma Ikuo Tsunoda Yasuhiro Mitamura Keiji |
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Institution: | Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai Shinagawa-ku, 142-8666, Tokyo, Japan. |
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Abstract: | In isolated rat pancreatic acini, protein expression of RhoA and Rho-associated kinase, ROCK-II, and the formation of immunocomplex of RhoA with ROCK-II were enhanced by CCK-8, carbachol, and the phorbol ester TPA. The ROCK-specific inhibitor, Y-27632, did not alter basal amylase secretion, whereas it potentiated CCK-stimulated pancreatic enzyme secretion in vitro. During caerulein-induced pancreatitis occurring in mice in vivo, Y-27632 enhanced serum amylase levels and the formation of interstitial edema and vacuolization at 12-18h after the first injection of caerulein. Y-27632 in turn inhibited the recovery of protein expression of ROCK-II at 18h after the first caerulein injection. These results suggest that RhoA and ROCK-II assemble normal CCK-stimulated pancreatic enzyme secretion and prevent caerulein-induced acute pancreatitis. |
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Keywords: | RhoA ROCK-II Pancreatitis Cytoskeleton Rat and mouse |
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