Leukotriene B4 Inhibits L-Type Calcium Channels via p38 Signaling Pathway in Vascular Smooth Muscle Cells

Abstract

Background/Aims: 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 Ca_V1.2 was determined by Real-time RT-PCR. The protein expression of Ca_V1.2 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 Ca_V1.2 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-κB kinase had no effects on LTB₄ inhibition of L-type calcium channel currents in A7r5 cells. Conclusion: 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.