TY - JOUR
T1 - Novel effect of N-palmitoyl-l-serine phosphoric acid on cytosolic Ca 2+ levels in human osteoblasts
AU - Jan, Chung Ren
AU - Lu, Yih Chau
AU - Jiann, Bang Ping
AU - Chang, Hong Tai
AU - Wang, Jue Long
AU - Chen, Wei Chung
AU - Huang, Jong Khing
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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 μM) caused a rapid and transient plateau [Ca2+]i rise in a concentration-dependent marmer (EC50=0.5 μM). 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 [Ca 2+]i rise. U73122, an inhibitor of phospholipase C, abolished histamine (but not L-NASPA)-induced [Ca2+]i rise. Overnight incubation with 1 μM L-NASPA did not affect cell proliferation, but 10-20 μM 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.
AB - 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 μM) caused a rapid and transient plateau [Ca2+]i rise in a concentration-dependent marmer (EC50=0.5 μM). 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 [Ca 2+]i rise. U73122, an inhibitor of phospholipase C, abolished histamine (but not L-NASPA)-induced [Ca2+]i rise. Overnight incubation with 1 μM L-NASPA did not affect cell proliferation, but 10-20 μM 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.
UR - http://www.scopus.com/inward/record.url?scp=0041695352&partnerID=8YFLogxK
U2 - 10.1034/j.1600-0773.2003.930203.x
DO - 10.1034/j.1600-0773.2003.930203.x
M3 - 文章
C2 - 12899668
AN - SCOPUS:0041695352
SN - 0901-9928
VL - 93
SP - 71
EP - 76
JO - Pharmacology and Toxicology
JF - Pharmacology and Toxicology
IS - 2
ER -