Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Madin-Darby canine kidney (MDCK) cells, the effect of maprotiline, an antidepressant, on intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured using fura-2. Maprotiline (> 2.5 microM) caused a rapid rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50) 200 microM). Maprotiline-induced [Ca(2+)](i) rise was reduced by removal of extracellular Ca(2+) or by addition of La(3+), but was not altered by voltage-gated Ca(2+)-channel blockers. Maprotiline-induced Mn(2+) influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca(2+) influx. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic [Ca(2+)](i) rise, after which the increasing effect of maprotiline on [Ca(2+)](i) was nearly abolished; also, pretreatment with maprotiline reduced a portion of thapsigargin-induced [Ca(2+)](i) rise. U73122, an inhibitor of phospholipase C, abolished [Ca(2+)](i) rise induced by ATP (but not by maprotiline). Overnight incubation with 1-10 microM maprotiline enhanced cell viability, but 20-50 microM maprotiline decreased it. These findings suggest that maprotiline rapidly increases [Ca(2+)](i) in renal tubular cells by stimulating both extracellular Ca(2+) influx and intracellular Ca(2+) release, and may modulate cell proliferation in a concentration-dependent manner.
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PMID:Effect of the antidepressant maprotiline on calcium movement and the viability of renal tubular cells. 1505 8

In human neuroblastoma IMR32 cells, the effect of the anti-depressant maprotiline on baseline intracellular Ca2+ concentrations ([Ca2+]i) was explored by using the Ca2+-sensitive probe fura-2. Maprotiline at concentrations greater than 100 microM caused a rapid rise in [Ca2+]i in a concentration-dependent manner (EC50 = 200 microM). Maprotiline-induced [Ca2+]i rise was reduced by 50% by removal of extracellular Ca2+. Maprotiline-induced [Ca2+]i rises were inhibited by half by nifedipine, but was unaffected by verapamil or diiltiazem. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, caused a monophasic [Ca2+]i rise, after which the increasing effect of maprotiline on [Ca2+]i was abolished. U73122, an inhibitor of phospholipase C, did not affect maprotiline-induced [Ca2+]i rises. These findings suggest that in human neuroblastoma cells, maprotiline increases [Ca2+]i by stimulating extracellular Ca2+ influx and also by causing intracellular Ca2+ release from the endoplasmic reticulum via a phospholiase C-independent manner.
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PMID:Effect of maprotiline on Ca(2+) movement in human neuroblastoma cells. 1520 57

1. The effect of maprotiline, an antidepressant, on human prostate cells is unclear. In the present study, the effect of maprotiline on [Ca2+]i and growth in PC3 human prostate cancer cells was measured using the fluorescent dyes fura-2 and tetrazolium, respectively. 2. Maprotiline caused a rapid, concentration-dependent increase in [Ca2+]i (EC50 = 200 micromol/L). The maprotiline-induced [Ca2+]i increase was reduced by removal of extracellular Ca2+ or pretreatment with nicardipine. 3. The maprotiline-induced Mn2+ influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca2+ influx. 4. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic [Ca2+]i increase, after which the effects of maprotiline of increasing [Ca2+]i were abolished. In addition, pretreatment with maprotiline reduced a major portion of the thapsigargin-induced increase in [Ca2+]i. 5. U73122, an inhibitor of phospholipase C, abolished the ATP (but not maprotiline)-induced increase in [Ca2+]i. 6. Overnight incubation with 1-10 micromol/L maprotiline did not alter cell proliferation, although incubation with 30-50 micromol/L maprotiline decreased cell proliferation. 7, These findings suggest that maprotiline rapidly increases [Ca2+]i in human prostate cancer cells by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release and that it may modulate cell proliferation in a concentration-dependent manner.
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PMID:Effect of the antidepressant maprotiline on Ca2+ movement and proliferation in human prostate cancer cells. 1523 32