title: [Lysophosphatidic acid activates L-arginine/nitric oxide pathway of platelets in rats].
abstract: 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.
authors.affiliation: Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yu-ying
authors.initials: YY
authors.lastname: Cui
authors.forename: Li-ke
authors.initials: LK
authors.lastname: Zhang
authors.forename: Qi-zhuan
authors.initials: QZ
authors.lastname: Wu
authors.forename: Hong-feng
authors.initials: HF
authors.lastname: Jiang
authors.forename: Chao-shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; C032881:lysophosphatidic acid; D019331:NG-Nitroarginine Methyl Ester