Alterations in alveolar type II cell metabolism induced by tetrandrine and other alkaloids.
Miles-PR; Bowman-L; Ma-JK; Ma-JY
Toxicol Appl Pharmacol 1993 Mar; 119(1):142-149
Cellular and mitochondrial ATP production and oxygen consumption were examined in isolated rat alveolar type-II cells following exposure to the bisbenzylisoquinoline alkaloid tetrandrine (518343) (TT), which has been used in treating fibrotic lung diseases in China. Also examined was the question as to whether or not intracellular calcium levels may be important in the TT observed effects. Alveolar type-II cells were isolated from the lungs of male Sprague-Dawley-rats, and tests were conducted in untreated cells and in cells exposed to bisbenzylisoquinoline alkaloids, the oxidative phosphorylation uncoupler carbonyl-cyanide-m- chlorophenylhydrazone or 4-bromo-A-23187 (a calcium ionophore). Results indicated that TT and other bisbenzylisoquinoline alkaloids are able to change the metabolism of isolated alveolar type-II cells. The most significant effect appeared to be a reduced level of cellular ATP in the exposed cells. This may be caused by an alkaloid induced increase in the intracellular calcium concentration. The authors suggest that the increased internal calcium may result in a reduction in mitochondrial ATP formation with no effect on mitochondrial oxygen consumption. The overall effect is a reduced cellular ATP level and subsequent impaired ability of type-II cells to perform normal functions.
NIOSH-Author; In-vitro-studies; Respiratory-system-disorders; Laboratory-animals; Alveolar-cells; Pharmaceuticals; Pulmonary-system; Therapeutic-agents
Toxicology and Applied Pharmacology