The phospholipase C inhibitor U73122 increases cytosolic calcium in MDCK cells by activating calcium influx and releasing stored calcium

被引:59
作者
Jan, CR
Ho, CM
Wu, SN
Tseng, CJ
机构
[1] Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung 813, Taiwan
[2] Natl Sun Yat Sen Univ, Dept Biol, Kaohsiung 813, Taiwan
[3] Natl Sun Yat Sen Univ, Inst Life Sci, Kaohsiung 813, Taiwan
关键词
MDCK cells; U73122; phospholipase C; calcium stores; fura-2;
D O I
10.1016/S0024-3205(98)00346-4
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 mu M 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 Ca-2 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.
引用
收藏
页码:895 / 908
页数:14
相关论文
共 33 条
  • [1] DIFFERENTIAL-EFFECTS OF PHORBOL ESTERS ON PGE2 AND BRADYKININ-INDUCED ELEVATION OF [CAI2+] IN MDCK-CELLS
    ABOOLIAN, A
    VANDERMOLEN, M
    NORD, EP
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (06): : F1135 - F1143
  • [2] [Anonymous], 1993, NEUROPROTOCOLS, V3, P125, DOI 10.1006/ncmn.1993.1046
  • [3] Elementary and global aspects of calcium signalling
    Berridge, MJ
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1997, 499 (02): : 291 - 306
  • [4] BLEASDALE JE, 1990, J PHARMACOL EXP THER, V255, P756
  • [5] CALCIUM SIGNALING
    CLAPHAM, DE
    [J]. CELL, 1995, 80 (02) : 259 - 268
  • [6] DEMAUREX N, 1992, J BIOL CHEM, V267, P2318
  • [7] DEMOEL MP, 1995, EUR J BIOCHEM, V234, P626
  • [8] Two different store-operated Ca2+ entry pathways in MDCK cells
    Dietl, P
    Haller, T
    Wirleitner, B
    Friedrich, F
    [J]. CELL CALCIUM, 1996, 20 (01) : 11 - 19
  • [9] ACTIVATION OF POTASSIUM CHANNELS IN RENAL EPITHELIOID CELLS (MDCK) BY EXTRACELLULAR ATP
    FRIEDRICH, F
    WEISS, H
    PAULMICHL, M
    LANG, F
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (05): : C1016 - C1021
  • [10] GRYNKIEWICZ G, 1985, J BIOL CHEM, V260, P3440