期刊
ANESTHESIOLOGY
卷 118, 期 5, 页码 1065-1075出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ALN.0b013e31828e180e
关键词
-
资金
- Canadian Institutes of Health Research (Ottawa, Ontario, Canada) [MOB-84517]
Background: Volatile anesthetics act primarily through upregulating the activity of gamma-aminobutyric acid type A (GABA(A)) receptors. They also exhibit antiinflammatory actions in the lung. Rodent alveolar type II (ATII) epithelial cells express GABA(A) receptors and the inflammatory factor cyclooxygenase- 2 (COX-2). The goal of this study was to determine whether human ATII cells also express GABA(A) receptors and whether volatile anesthetics upregulate GABA(A) receptor activity, thereby reducing the expression of COX-2 in ATII cells. Methods: The expression of GABA(A) receptor subunits and COX-2 in ATII cells of human lung tissue and in the human ATII cell line A549 was studied with immunostaining and immunoblot analyses. Patch clamp recordings were used to study the functional and pharmacological properties of GABA(A) receptors in cultured A549 cells. Results: ATII cells in human lungs and cultured A549 cells expressed GABA(A) receptor subunits and COX-2. GABA induced currents in A549 cells, with half-maximal effective concentration of 2.5 mu(M). Isoflurane (0.1-250 mu(M)) enhanced the GABA currents, which were partially inhibited by bicuculline. Treating A549 cells with muscimol or with isoflurane (250 mu(M)) reduced the expression of COX-2, an effect that was attenuated by cotreatment with bicuculline. Conclusions: GABA(A) receptors expressed by human ATII cells differ pharmacologically from those in neurons, exhibiting a higher affinity for GABA and lower sensitivity to bicuculline. Clinically relevant concentrations of isoflurane increased the activity of GABA(A) receptors and reduced the expression of COX-2 in ATII cells. These findings reveal a novel mechanism that could contribute to the antiinflammatory effect of isoflurane in the human lung.
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