Publication Date:
1987-05-22
Description:
Electrical coupling and dye coupling between pairs of rat hepatocytes were reversibly reduced by brief exposure to halogenated methanes (CBrCl3, CCl4, and CHCl3). The potency of different halomethanes in uncoupling hepatocytes was comparable to their hepatotoxicity in vivo, and the rank order was the same as that of their tendency to form free radicals. The effect of carbon tetrachloride (CCl4) on hepatocytes was substantially reduced by prior treatment with SKF 525A, an inhibitor of cytochrome P-450, and by exposure to the reducing reagent beta-mercaptoethanol. Halomethane uncoupling occurred with or without extracellular calcium and did not change intracellular concentrations of calcium and hydrogen ions or the phosphorylation state of the main gap-junctional protein. Thus the uncoupling appears to depend on cytochrome P-450 oxidative metabolism in which free radicals are generated and may result from oxidation of the gap-junctional protein or of a regulatory molecule that leads to closure of gap-junctional channels. Decreases in junctional conductance may be a rapid cellular response to injury that protects healthy cells by uncoupling them from unhealthy ones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saez, J C -- Bennett, M V -- Spray, D C -- GM 30667/GM/NIGMS NIH HHS/ -- NS 07512/NS/NINDS NIH HHS/ -- NS 16424/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1987 May 22;236(4804):967-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3576214" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bromotrichloromethane/toxicity
;
Carbon Tetrachloride/*toxicity
;
Carbon Tetrachloride Poisoning/*physiopathology
;
Chloroform/toxicity
;
Electric Conductivity
;
Intercellular Junctions/drug effects/*physiology
;
Liver/drug effects/pathology/*physiopathology
;
Rats
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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