Jan C R, Ho C M, Wu S N, Tseng C J
Department of Medical Education and Research, Veterans General Hospital-Kaohsiung, National Sun Yat-Sen University, Taiwan, ROC.
Life Sci. 1998;63(10):895-908. doi: 10.1016/s0024-3205(98)00346-4.
The effects of the phospholipase C (PLC) inhibitor U73122 on intracellular calcium levels ([Ca2+]i) were studied in MDCK cells. U73122 elevated [Ca2+]i dose-dependently. Ca2+ influx contributed to 75% of 20 microM U73122-induced Ca2+ signals. U73122 pretreatment abolished the [Ca2+]i transients evoked by ATP and bradykinin, suggesting that U73122 inhibited PLC. The Ca2+ signals among individual cells varied considerably. The internal Ca2+ source for the U73122 response was the endoplasmic reticulum (ER) since the response was abolished by thapsigargin. The depletion of the ER Ca2+ store triggered a La3+-sensitive capacitative Ca2+ entry. Independently of the internal release and capacitative Ca2 entry, U73122 directly evoked Ca2+ influx through a La3+-insensitive pathway. The U73122 response was augmented by pretreatment of carbonylcyanide m-chlorophynylhydrozone (CCCP), but not by Na+ removal, implicating that mitochondria contributed significantly in buffering the Ca2+ signal, and that efflux via Na+/Ca2+ exchange was insignificant.
在MDCK细胞中研究了磷脂酶C（PLC）抑制剂U73122对细胞内钙水平（[Ca2+]i）的影响。U73122剂量依赖性地升高[Ca2+]i。Ca2+内流对20微摩尔U73122诱导的Ca2+信号的贡献率为75%。U73122预处理消除了ATP和缓激肽诱发的[Ca2+]i瞬变，提示U73122抑制PLC。单个细胞间的Ca2+信号差异很大。U73122反应的细胞内钙来源是内质网（ER），因为该反应被毒胡萝卜素消除。内质网钙库耗竭触发了镧敏感的容量性钙内流。不依赖于细胞内钙释放和容量性钙内流，U73122通过一条镧不敏感途径直接诱发Ca2+内流。羰基氰化物间氯苯腙（CCCP）预处理增强了U73122反应，但去除Na+则无此作用，这表明线粒体在缓冲Ca2+信号方面起重要作用，且通过Na+/Ca2+交换的外流作用不明显。
