Harris R A, Pon D J, Katz S, Hanrahan J W
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Am J Physiol. 1997 Aug;273(2 Pt 1):L363-73. doi: 10.1152/ajplung.1997.273.2.L363.
We studied the intracellular free Ca2+ concentration ([Ca2+]i) response to histamine in a cystic fibrosis airway epithelial cell line (CF/T43). Histamine (100 microM; duration approximately 10 min) biphasically increased [Ca2+]i, with a rapid initial peak (30-45 s) followed by a smaller second peak that lasted for several minutes before returning to baseline. Neither peak specifically depended on Ca2+ influx. Exposure to bradykinin (10 microM) elicited a single peak that lasted 3-3.5 min before returning to baseline. Bradykinin increased intracellular inositol 1,4,5-trisphosphate (IP3), which peaked and returned to baseline within 150 s. Histamine also increased IP3 monophasically, but the peak was brief (< 20 s). Both phases of the Ca2+ response to histamine exhibited similar responsiveness to histamine concentration and sensitivity to antagonists. Cimetidine or thioperamide (1 mM) had no effect on the second peak. Pyrilamine blocked the second peak at concentrations similar to those required to block the initial peak. Activation of the second peak was observed at a threshold concentration of 1 microM comparable with the threshold of the initial peak. Neither adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic monophosphate, nor cyclic ADP (cADP)-ribose altered the second phase of the histamine response.
我们研究了囊性纤维化气道上皮细胞系（CF/T43）中细胞内游离钙离子浓度（[Ca2+]i）对组胺的反应。组胺（100微摩尔；持续时间约10分钟）双相性地增加[Ca2+]i，先是快速出现一个初始峰值（30 - 45秒），随后是一个较小的第二个峰值，该峰值持续几分钟后才恢复到基线水平。两个峰值均不特别依赖于钙离子内流。暴露于缓激肽（10微摩尔）会引发一个持续3 - 3.5分钟的单一峰值，然后恢复到基线水平。缓激肽增加细胞内肌醇1,4,5 - 三磷酸（IP3），其在150秒内达到峰值并恢复到基线水平。组胺也单相性地增加IP3，但峰值很短暂（<20秒）。组胺引起的钙离子反应的两个阶段对组胺浓度表现出相似的反应性以及对拮抗剂的敏感性。西咪替丁或硫代哌酰胺（1毫摩尔）对第二个峰值没有影响。吡苄明在与阻断初始峰值所需浓度相似的情况下阻断了第二个峰值。在1微摩尔的阈值浓度下观察到第二个峰值的激活，这与初始峰值的阈值相当。腺苷3',5'-环磷酸、鸟苷3',5'-环磷酸或环ADP（cADP）-核糖均未改变组胺反应的第二阶段。
