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Participation of Phosphoinositides in Gastric Mucosal Protection by Colloidal Bismuth Subcitrate against Ethanol‐Induced Injury
Author(s) -
Slomiany Bronislaw L.,
Wang Xiaoying,
Palecz Danuta,
Okazaki Kazuichi,
Slomiany Amalia
Publication year - 1990
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1990.tb01205.x
Subject(s) - mucin , in vivo , ethanol , chemistry , in vitro , gastric mucosa , pharmacology , saline , stomach , biochemistry , endocrinology , medicine , biology , microbiology and biotechnology
The mechanism of gastric mucosal protection by an antiulcer agent, colloidal bismuth subcitrate (CBS), against ethanol‐induced injury was investigated using in vivo and in vitro systems. The experiments in vivo were conducted with groups of rats with and without indomethacin pretreatment, and the animals received either a dose of CBS (100 mg/kg) or a vehicle (saline), followed 30 min later by ethanol. In the in vitro studies, gastric mucosa segments were cultured in the presence of CBS, ethanol, or both. The results of in vivo experiments revealed that in the absence of CBS, ethanol caused extensive gastric hemorrhagic lesions which were significantly reduced following CBS pretreatment and this effect of CBS was not prevented by indomethacin. The data obtained with gastric mucosal culture established that in comparison to the controls, ethanol caused a 27% decrease in mucin synthesis, while mucin synthesis in the presence of CBS increased by 48%. The increase in mucin synthesis evoked by CBS was accompanied by the enhanced metabolism of mucosal phosphoinositides, as reflected by a decrease in PI (15%) and PIP 2 (30%), and an increase in IP 1 (26%) and IP 3 (67%). In contrast, ethanol, which exhibited detrimental effect on mucin synthesis, caused a decrease in PIP (35%), IP 2 (47%) and IP 3 (38%), and an increase in PIP 2 (80%), and IP 1 (51%). However, when the mucosal culture was carried out in the presence of both CBS and ethanol, the detrimental changes evoked by ethanol on mucin synthesis were prevented, and the phosphoinositide and inositide phosphate distribution patterns were quite similar to those in the mucosa cultured in the presence of CBS only. The results indicate that CBS is capable of overcoming the untoward effect of ethanol on phosphoinositide‐specific phospholipase C, thus restoring phosphoinositide‐derived messenger molecule metabolism essential for cellular proliferation and mucus synthesis, the key factors in gastric mucosal defense.