[Lysophosphatidic acid activates L-arginine/nitric oxide pathway of platelets in rats].
OBJECTIVE
To investigate the mechanism of platelet function caused by Lysophosphatidic acid (LPA), by observing the change of the L-arginine/nitric oxide synthase/nitric oxide (L-Arg/NOS/NO) pathway of platelet in rats.


METHODS
LPA (10(-6), 10(-5) and 5x10(-5) mol/L) was administrated in rats and incubated for 30 and 60 minutes. The nitrite production was measured by Greiss assay; NOS activities and L-arginine transportation were detected by isotope tracer method and intracellular [Ca(2+)]i changes by fluorescent probe.


RESULTS
LPA increased NO release by 35% and 56%, after incubating for 30 and 60 minutes, respectively. LPA (10(-6), 10(-5)aand 5x10(-5) mol/L) enhanced the NO productions of platelets in a concentration-dependent manner (P<0.01). EC(50) was 17.8 micromol/L, and 95% CI was 13.3-24.2 micromol/L, involved in the physiological concentration of LPA in plasma (P<0.01). Simultaneously, different doses of LPA increased NOS activities and L-arginine uptake in a dose-dependent manner (P<0.01). In this study, LPA (50 micromol/L) increased the intracellular free calcium ion concentration ([Ca(2+)]i, P<0.01), after incubating for 30 and 60 minutes. Pre-treated with NOS inhibitor-L-NAME for 20 minutes, LPA obviously enhanced the effects by 20% and 32% respectively (P<0.01). On the contrary, pre-treated with L-arginine (200 micromol/L) for the same times obviously reduced the effects by 14% and 18% respectively (P<0.01).


CONCLUSIONS
LPA increased NO release by enhancing L-arginine uptake and NOS activities, up-regulating L-arginine/NOS/NO pathway in platelets of rats.
Cui
Yu-ying
YY
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Zhang
Li-ke
LK
Wu
Qi-zhuan
QZ
Jiang
Hong-feng
HF
Tang
Chao-shu
CS
Geng
Bin
B
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; C032881:lysophosphatidic acid; D019331:NG-Nitroarginine Methyl Ester