Effect of m-3M3FBS on Ca(2+) movement in Madin-Darby canine renal tubular cells.
The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide (m-3M3FBS), a presumed phospholipase C (PLC) activator, on cytosolic free Ca(2+) concentrations ([Ca( 2+)](i)) in Madin-Darby canine kidney (MDCK) cells is unclear. This study explored whether m-3M3FBS changed basal [Ca(2+)](i) levels in suspended MDCK cells using fura-2 as a Ca(2+)-sensitive fluorescent dye. M-3M3FBS at concentrations between 0.1 and 20 microM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was decreased by removing extracellular Ca(2+). M-3M3FBS-induced Ca(2+) influx was inhibited by the store-operated Ca(2+) channel blockers nifedipine, econazole, and SK&F96365, and by the phospholipase A2 inhibitor aristolochic acid. In Ca(2+)-free medium, 20-microM m-3M3FBS pretreatment abolished the [Ca(2+)](i) rise induced by the endoplasmic reticulum Ca(2+) pump inhibitors thapsigargin (TG) and cyclopiazonic acid (CPA). Conversely, pretreatment with TG or CPA partly reduced m-3M3FBS-induced [Ca(2+)](i) rise. The inhibition of PLC with U73122 did not alter m-3M3FBS-induced [Ca(2+)](i) rise. Collectively, in MDCK cells, m-3M3FBS induced [Ca(2+)](i) rises by causing PLC-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx via store-operated Ca(2+) channels and other unidentified Ca(2+) channels.
Fang
Yi-Chien
YC
Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan.
Kuo
Daih-Huang
DH
Shieh
Pochuen
P
Chen
Fu-An
FA
Kuo
Chun-Chi
CC
Jan
Chung-Ren
CR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry; D016257:Fura-2 / Q000737:chemistry; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D016257:Fura-2; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2; D013449:Sulfonamides; C473783:2,4,6-trimethyl-N-(meta-3-trifluoromethylphenyl)benzenesulfonamide; D000096926:Benzenesulfonamides