Deactivation of ROCK-II by Y-27632 enhances basolateral pancreatic enzyme secretion and acute pancreatitis induced by CCK analogues.
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.
Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai Shinagawa-ku, 142-8666, Tokyo, Japan.
Kazushige
K
Kusama
Fumihiko
F
Nozu
Toshinari
T
Awai
Shigeki
S
Tanaka
Ikuo
I
Honma
Yasuhiro
Y
Tsunoda
Keiji
K
Mitamura
D000208:Acute Disease; D000577:Amides / Q000494:pharmacology*; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D016764:Cell Polarity; D002478:Cells, Cultured; D002108:Ceruletide; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D010179:Pancreas / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism / Q000502:physiology
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D002108:Ceruletide; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000681:Amylases; D020742:rhoA GTP-Binding Protein