Mechanism of bifonazole-induced [Ca2+]i increases in MDCK renal tubular cells.
The effect of the antifungal drug bifonazole on Ca2+ homeostasis in Madin Darby canine kidney (MDCK) cells was investigated. Cell suspensions were loaded with the Ca2+-sensitive dye fura-2, and the fluorescence changes were measured with a spectrofluorophotometer. At concentrations between 10-80 microM bifonazole increased cytosolic free Ca2+ levels ([Ca2+]i) in a concentration-dependent manner. The Ca2+ signals were partly inhibited by removing extracellular Ca2+. Bifonazole (40 microM) released Ca2+ from the store sensitive to 1 microM thapsigargin, an endopolasmic reticulum Ca2+ pump inhibitor. Bifonazole (40 microM) per se induced capacitative Ca2+ entry while reduced 1 microM thapsigargin-induced capacitative Ca2+ entry. Inositol 1,4,5-trisphosphate may be involved in bifonazole-induced Ca2+ release because inhibiting phospholipase C with 2 microM U73122 partly reduced the bifonazole response. Together, bifonazole increased [Ca2+]i in renal tubular cells by inducing intracellular Ca2+ release and extracellular Ca2+ influx.
Cho
K J
KJ
Department of Medicine, Kaohsiung Veterans General Hospital, Taipei, Taiwan, ROC.
Su
W
W
Chen
W C
WC
Law
Y P
YP
Fang
H C
HC
Liu
C P
CP
Cheng
J S
JS
Lee
K C
KC
Lo
Y K
YK
Chang
H T
HT
Huang
J K
JK
Jan
C R
CR
D000255:Adenosine Triphosphate / Q000008:administration & dosage; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007684:Kidney Tubules / Q000166:cytology* / Q000378:metabolism*; D023421:Models, Animal; D019284:Thapsigargin / Q000008:administration & dosage; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000187:drug effects
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; C036596:bifonazole; D002118:Calcium