Effect of the antidepressant sertraline on Ca2+ fluxes in Madin-Darby canine renal tubular cells.
The effect of the antidepressant sertraline on cytosolic-free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells is unclear. This study explored whether sertraline changed basal [Ca2+]i levels in suspended MDCK cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Sertraline at concentrations between 1 and 100 microM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+ implicating Ca2+ entry and release both contributed to the [Ca2+]i rise. Sertraline induced Mn2+ influx, leading to quench of fura-2 fluorescence, suggesting Ca2+ influx. This Ca2+ influx was inhibited by suppression of phospholipase A2 but not by store-operated Ca2+ channel blockers and protein kinase C/A modulators. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitors nearly abolished sertraline-induced Ca2+ release. Conversely, pretreatment with sertraline partly reduced inhibitor-induced [Ca2+]i rise, suggesting that sertraline released Ca2+ from endoplasmic reticulum. Inhibition of phospholipase C did not much alter sertraline-induced [Ca2+]i rise. Collectively, in MDCK cells, sertraline induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-sensitive Ca2+ channels.
Huang
Chun-Jen
CJ
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Kuo
Daih-Huang
DH
Chang
Kai-Hsien
KH
Shieh
Pochuen
P
Chen
Fu-An
FA
Fang
Yi-Chien
YC
Kuo
Chun-Chi
CC
Jan
Chung-Ren
CR
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D004285:Dogs; 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*; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000928:Antidepressive Agents; D002118:Calcium; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D016257:Fura-2; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D010738:Type C Phospholipases