title: Leukotriene B4 Inhibits L-Type Calcium Channels via p38 Signaling Pathway in Vascular Smooth Muscle Cells.
abstract: OBJECTIVE
  Arachidonic acid (AA) and its metabolites are important endogenous lipid messengers. In this study, we test the effect of Leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of AA, on L-type calcium channels in A7r5 rat aortic vascular smooth muscle cells.
  
  
  METHODS
  L-type calcium channel currents were recorded by a patch-clamp technique. The mRNA expression of CaV1.2 was determined by Real-time RT-PCR. The protein expression of CaV1.2 and p38 activity was determined by Western blot analysis.
  
  
  RESULTS
  LTB4 inhibits L-type channel currents in A7r5 cells in a dose-and time- dependent manner. LTB4 reduced the mRNA/protein expression of CaV1.2 channels in A7r5 cells. BLT1 receptor antagonist LY29311 abrogated the inhibitory effect of LTB4, while BLT2 receptor antagonist LY255283 had no effect. 5Z-7-oxozeaenol and SB203580, which block TAK1 and p38 kinase respectively, abrogated the LTB4 inhibitory effect on L-type calcium channels. LTB4 increased p38 activity in A7r5 cells. Blockage of Src, PI3K, JNK and NF-x03BA;B kinase had no effects on LTB4 inhibition of L-type calcium channel currents in A7r5 cells.
  
  
  CONCLUSIONS
  We conclude that LTB4 inhibits L-type calcium channels through BLT1-TAk1-p38 signaling pathway. The LTB4 inhibitory effect on L-type calcium channels may be involved in its pathological processes such as atherosclerosis.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.forename: Tingting
authors.initials: T
authors.lastname: Yang
authors.forename: Langxi
authors.initials: L
authors.lastname: Miao
authors.forename: Yan-Ai
authors.initials: YA
authors.lastname: Mei
authors.forename: Changlong
authors.initials: C
authors.lastname: Hu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D001565:Benzoates; D020746:Calcium Channels, L-Type; D007093:Imidazoles; D007975:Leukotriene B4; D020930:MAP Kinase Kinase Kinases; D011725:Pyridines; D012333:RNA, Messenger; D018102:Receptors, Leukotriene B4; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7; C094099:LY 293111; C093642:SB 203580