Novel effect of N-palmitoyl-L-serine phosphoric acid on cytosolic Ca2+ levels in human osteoblasts.
The effect of N-palmitoyl-L-serine phosphoric acid (L-NASPA), which has been used as an inhibitor of lysophosphatidic acid receptors, on intracellular Ca2+ concentration ([Ca2+]i) in human osteosarcoma MG63 cells was measured by using fura-2. L-NASPA (0.1-10 microM) caused a rapid and transient plateau [Ca2+]i rise in a concentration-dependent manner (EC50=0.5 microM). The L-NASPA-induced [Ca2+]i rise was partly reduced by removal of extracellular Ca2+ but was not altered by L-type voltage-gated Ca2+ channel blockers. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, induced a [Ca2+]i rise, after which the increasing effect of L-NASPA on [Ca2+]i was completely inhibited; also, pretreatment with L-NASPA partly reduced thapsigargin-induced [Ca2+]i rise. U73122, an inhibitor of phospholipase C, abolished histamine (but not L-NASPA)-induced [Ca2+]i rise. Overnight incubation with 1 microM L-NASPA did not affect cell proliferation, but 10-20 microM L-NASPA exerted 4% and 15% inhibition, respectively. Collectively, L-NASPA rapidly increased [Ca2+]i in MG63 cells by evoking both extracellular Ca2+ influx and intracellular Ca2+ release, and is cytotoxic at higher concentrations.
Jan
Chung-Ren
CR
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813.
Lu
Yih-Chau
YC
Jiann
Bang-Ping
BP
Chang
Hong-Tai
HT
Wang
Jue-Long
JL
Chen
Wei-Chung
WC
Huang
Jong-Khing
JK
D000818:Animals; D002118:Calcium / Q000737:chemistry* / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002417:Cattle; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology*; D010740:Phospholipases / Q000378:metabolism; D010768:Phosphoserine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D005456:Fluorescent Dyes; C101516:N-palmitoylserine phosphoric acid; D010168:Palmitates; D010768:Phosphoserine; D010740:Phospholipases; D002118:Calcium; D016257:Fura-2