Salari H, Yeung M, Howard S, Schellenberg R R
Jack Bell Research Centre, Department of Medicine, Vancouver, British Columbia, Canada.
J Allergy Clin Immunol. 1992 Dec;90(6 Pt 1):918-26. doi: 10.1016/0091-6749(92)90464-d.
Tracheal smooth muscle from guinea pigs with documented airway hyperresponsiveness in vivo after multiple antigen challenges produced 30% to 50% greater force than tracheas from control guinea pigs, when stimulated with carbachol, histamine, or leukotriene D4. When cultured smooth muscle cells were incubated with myo[2-3H]inositol, basal uptake of [3H]inositol was similar in cells from normal and hyperresponsive guinea pigs, but when these cells were stimulated with contractile agonists, there was increased uptake of inositol in hyperresponsive cells. Analysis of inositol phosphates by column chromatography and high-performance liquid chromatography revealed the presence of inositol-1,4,5-triphosphate, inositol-1,3,4-trisphosphate, inositol-1,4-bisphosphate, and inositol-1-monophosphate. The release of inositol-1,4,5-triphosphate, inositol-1,4-biphosphate, and inositol-1-monophosphate by smooth muscle cells stimulated with carbachol, leukotriene D4, or histamine was 20% to 40% greater in cells derived from hyperresponsive animals than cells from normal animals. These data demonstrate that the increased muscle contraction of hyperresponsive guinea pig tracheas is associated with increased inositol phosphate metabolism in these cells. Delineating the mechanisms of airway smooth muscle contraction should provide new pharmacologic targets for the inhibition of bronchoconstriction in asthma.
在多次抗原激发后体内有气道高反应性记录的豚鼠的气管平滑肌，在用卡巴胆碱、组胺或白三烯D4刺激时，产生的力量比对照豚鼠的气管大30%至50%。当培养的平滑肌细胞与肌醇[2-³H]一起孵育时，正常和高反应性豚鼠细胞中[³H]肌醇的基础摄取相似，但当这些细胞用收缩激动剂刺激时，高反应性细胞中肌醇的摄取增加。通过柱色谱和高效液相色谱分析肌醇磷酸酯，发现存在肌醇-1,4,5-三磷酸、肌醇-1,3,4-三磷酸、肌醇-1,4-二磷酸和肌醇-1-单磷酸。用卡巴胆碱、白三烯D4或组胺刺激的平滑肌细胞释放的肌醇-1,4,5-三磷酸、肌醇-1,4-二磷酸和肌醇-1-单磷酸，在来自高反应性动物的细胞中比来自正常动物的细胞高20%至40%。这些数据表明，高反应性豚鼠气管平滑肌收缩增加与这些细胞中肌醇磷酸酯代谢增加有关。阐明气道平滑肌收缩的机制应为哮喘中支气管收缩的抑制提供新的药理学靶点。
