Sumio Watanabe

Effects of rebamipide on bile acid-induced inhibition of gastric epithelial repair in a rabbit cell culture model

Background: Anti‐ulcer agents exert various functional effects on gastric epithelial cells.

ACTIVATED STELLATE (ITO) CELLS POSSESS VOLTAGE-ACTIVATED CALCIUM CURRENT

We previously reported stellate (Ito) cells possess voltage-activated Ca2+ current. The activation of stellate cells has been indicated to contribute to liver fibrosis and the regulation of hepatic hemodynamics. The aim of this study was to investigate the relationship between voltage-activated Ca2+ current and activation of stellate cells. Voltage-activated Ca2+ current in stellate cells isolated from rats were studied using whole-cell patch clamp technique. L-type voltage-activated Ca2+ current was hardly detected in stellate cells cultured for less than 9 days. Ca2+ current was detected 12.5 and 69% of cells at the 10th and 14th day of culture, respectively. BrdU incorporation indicated cell proliferation was recognized over 50% of cells at the 3rd and 5th day of culture, respectively, then decreased significantly in a time-dependent manner. On the other hand, the expression of alpha-smooth muscle actin indicated cell activation increased from 7th day of culture and collagen type I mRNA appeared remarkably in cells cultured for more than 10 days. In this study, we concluded L-type voltage-activated Ca2+ current was recognized in activated stellate (myofibroblast-like) cells.

Hepatic stellate cell contraction is inhibited by lipo-prostaglandin E1 in vitro

Prostaglandin E1 (PGE1) has been reported to have, experimentally and clinically, a protective effect against liver damage. This effect may result from the relaxation of hepatic stellate cells, whose contraction induces vasoconstriction of hepatic sinusoids. However, prostaglandins are unstable and a new drug delivery system is necessary to administer a sufficient amount of prostaglandin to achieve a protective effect in the liver. The aim of the study is to investigate the effects of lipo‐prostaglandin E1 (lipo‐PGE1) which has a novel drug delivery system on the stellate cell contraction induced by endothelin‐1 in vitro. Lipo‐PGE1 inhibited endothelin‐1‐induced stellate cell contraction in concentrations of 10, 30 and 50 ng/mL. Therefore, lipo‐PGE1 may show a cytoprotective effect in the liver through the relaxation of stellate cells and an increase in the hepatic sinusoidal blood flow.

Integrity of myosin light chain kinase is essential for Ito cell contraction

Hepatic sinusoidal Ito cells (fat storing cells) are believed to play a regulatory role on hepatic sinusoidal blood flow through their contraction. The detailed mechanism of contraction of Ito cells, however, is still unknown. The present study was undertaken to clarify the effect of new myosin light chain kinase inhibitor, wortmannin, on Ito cell contraction. Ito cells prepared from rat liver were cultured for 4 days before the study. The contraction of Ito cells, which was monitored and analysed by time‐lapse video tape recording, was triggered by addition of endothelin‐1. Wortmannin pretreatment for 1 h inhibited endothelin‐induced Ito cell contraction dose‐dependently. Therefore, the integrity of the actomyosin system is essential for Ito cell contraction and normal sinusoidal blood flow.