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S1P triggers cerebral vessel constriction through the store‐operated calcium entry pathway
Author(s) -
Hopson Kristen Park,
Truelove Jessica,
Wang Yumei,
Waeber Christian
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb425
Subject(s) - orai1 , vasoconstriction , vascular smooth muscle , microbiology and biotechnology , calcium signaling , constriction , chemistry , stim1 , receptor , medicine , signal transduction , endocrinology , calcium , biology , smooth muscle
Objective To characterize signaling pathways by which sphingosine‐1‐phosphate (S1P) modulates vascular tone. Methods The role of store‐operated calcium entry (SOCE) in S1P‐induced Ca 2+ entry in vascular smooth muscle cells (VSMCs) and vessel constriction was assessed using ratiometric Ca 2+ measurements, quantitative RT‐PCR and isolated arteries. Results In VSMCs, S1P triggered STIM1 puncta formation, and SOCE activated by S1P was inhibited by 2‐aminoethoxydiphenylborate (2‐APB), diethylstilbestrol and gadolinium. In VSMCs prepared from S1P 3 receptor knockout mice, the initial calcium rise triggered by S1P was abolished, but SOCE was still present suggesting that S1P acts via multiple signaling pathways. S1P‐induced SOCE was larger in proliferative than in contractile VSMCs, correlating with increases in STIM1, Orai1, S1P 1 and S1P 3 receptor mRNA. STIM1, S1P 1 and S1P 3 receptor mRNA expression were larger in freshly isolated brain vessels than in aorta. These data, and the fact that 2‐APB inhibits S1P‐induced cerebral artery constriction, suggest that SOCE modulates S1P‐induced vasoconstriction in vivo. Conclusion These data support a role for SOCE in S1P induced calcium entry and vessel constriction. The relationship between increased S1P signaling and SOCE in proliferative VSMCs suggests a role of S1P in disorders associated with vascular proliferation, such as atherosclerosis or vasospasm.