Effect of desipramine on Ca2+ levels and growth in renal tubular cells.
The in vitro effect of desipramine on renal tubular cell is unknown. In Madin-Darby canine kidney (MDCK) cells, the effect of desipramine on intracellular Ca2+ concentration ([Ca2+]i) was measured by using fura-2. Desipramine (>25 microM) caused a rapid and sustained rise of [Ca2+]i in a concentration-dependent manner (EC50=50 microM). Desipramine-induced [Ca2+]i rise was prevented by 40% by removal of extracellular Ca2+ but was not altered by L-type Ca2+ channel blockers. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, caused a monophasic [Ca2+]i rise, after which desipramine failed to release more Ca2+; in addition, pretreatment with desipramine partly decreased thapsigargin-induced [Ca2+]i increase. U73122, an inhibitor of phospholipase C, did not change desipramine-induced [Ca2+]i rise. Incubation with 10-100 microM desipramine enhances or inhibits cell proliferation in a concentration- and time-dependent manner. The inhibitory effect of desipramine on proliferation was not extracellular Ca2+-dependent. Apoptosis appears to contribute to desipramine-induced cell death. Together, these findings suggest that desipramine increases baseline [Ca2+]i in renal tubular cells by evoking both extracellular Ca2+ influx and intracellular Ca2+ release, and can cause apoptosis.
Ho
Chin-Man
CM
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
Kuo
Soong-Yu
SY
Chen
Ching-Hsein
CH
Huang
Jong-Khing
JK
Jan
Chung-Ren
CR
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020013:Calcium Signaling; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors; D010738:Type C Phospholipases / Q000502:physiology
D000928:Antidepressive Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D005456:Fluorescent Dyes; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium; D003891:Desipramine; D016257:Fura-2