Sphingosine 1-phosphate increases an intracellular Ca2+ concentration via S1P3 receptor in cultured vascular smooth muscle cells

Fujii, K.; Machida, Takuji; Iizuka, Kenji; Hirafuji, Masahiko

doi:10.1111/jphp.12214

Cited by 15 publications

(10 citation statements)

References 37 publications

(50 reference statements)

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“…Although others suggest that calcium is vital to the chemerin signaling of immune cells [27, 31], hematopoietic [32] and mesenchymal stem cells [33], we are the first to link chemerin to the smooth muscle cell and to the L-type voltage gated calcium channel in any system. In both rat myocytes and vascular smooth muscle cells, L-type calcium channels have been linked to G i -protein mechanisms [34, 35], lending support to the finding that extracellular calcium is essential to chemerin-induced vasoconstriction.…”

Section: Discussionmentioning

confidence: 91%

Chemerin-induced arterial contraction is Gi- and calcium-dependent

Ferland

Darios

Neubig

et al. 2017

Vascular Pharmacology

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Chemerin is an adipokine associated with increased blood pressure, and may link obesity with hypertension. We tested the hypothesis that chemerin-induced contraction of the vasculature occurs via calcium flux in smooth muscle cells. Isometric contraction of rat aortic rings was performed in parallel with calcium kinetics of rat aortic smooth muscle cells to assess the possible signaling pathway. Chemerin-9 (nonapeptide of the chemerin S157 isoform) caused a concentration-dependent contraction of isolated aorta (EC50 100 nM) and elicited a concentration-dependent intracellular calcium response (EC50 10 nM). Pertussis toxin (Gi inhibitor), verapamil (L-type Ca2+ channel inhibitor), PP1 (Src inhibitor), and Y27632 (Rho kinase inhibitor) reduced both calcium influx and isometric contraction to chemerin-9 but PD098059 (Erk MAPK inhibitor) and U73122 (PLC inhibitor) had little to no effect on either measure of chemerin signaling. Although our primary aim was to examine chemerin signaling, we also highlight differences in the mechanisms of chemerin-9 and recombinant chemerin S157. These data support a chemerin-induced contractile mechanism in vascular smooth muscle that functions through Gi proteins to activate L-type Ca2+ channels, Src, and Rho kinase. There is mounting evidence linking chemerin to hypertension and this mechanism brings us closer to targeting chemerin as a form of therapy.

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Section: Discussionmentioning

confidence: 91%

Chemerin-induced arterial contraction is Gi- and calcium-dependent

Ferland

Darios

Neubig

et al. 2017

Vascular Pharmacology

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“…Considering that FTY720 has been endowed with a property of activation of S1P 3 receptors and activation of this receptor subtype has been linked to the increase in intracellular Ca 2+ concentration in cultured smooth muscle cells, it is thus tempting to speculate that the regulation of vascular tone in aorta by pretreatment with FTY720 could be ascribed to its action on S1P 3 receptors located in aortic smooth muscle cells (Karliner ; Fujii et al. ). One may argue that activation of S1P 1 receptors could also mediate FTY720‐related modulation of vascular contraction in aortic rings since FTY720 does bind potently to this S1P 1 receptor subtype (Karliner ).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to S1P-related vascular relaxation in aorta, pretreatment with FTY720 led to an enhancement of vascular contraction induced by high potassium or phenylephrine, an effect independent of endothelium. Considering that FTY720 has been endowed with a property of activation of S1P 3 receptors and activation of this receptor subtype has been linked to the increase in intracellular Ca 2+ concentration in cultured smooth muscle cells, it is thus tempting to speculate that the regulation of vascular tone in aorta by pretreatment with FTY720 could be ascribed to its action on S1P 3 receptors located in aortic smooth muscle cells (Karliner 2013;Fujii et al 2014). One may argue that activation of S1P 1 receptors could also mediate FTY720-related modulation of vascular contraction in Figure 5.…”

Section: Discussionmentioning

confidence: 99%

FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation

Zhao

Huo

Wang

et al. 2017

Pharmacology Res & Perspec

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Sphingosine 1‐phosphate (S1P) is an important signaling sphingolipid involved in the pathogenesis of various cardio cerebral vascular diseases such as ischemic stroke. In particular, the S1P mimetic FTY720 is protective for brain against ischemic conditions. However, whether and how FTY720 can modulate vascular tone and blood pressure remains to be determined. We showed that FTY720 (1 mg/kg) enhanced the contractile response of rat thoracic aortic rings induced by high potassium and phenylephrine, respectively. This enhancement involves the activation of extracellular signal‐regulated kinase (ERK) since ERK phosphorylation was also enhanced and application of PD98059 (10 μmol/L), an inhibitor of ERK activation abrogated the aforementioned enhanced response by FTY720. In parallel, FTY720 (1 mg/kg) led to a modest elevation of blood pressure in rats, effects also being prevented by PD98059. In contrast, FTY720 decreased the high potassium‐induced contractile response in basilarartery preparations from rabbits, an effect blocked by PD98059. Together, FTY720‐induced an enhanced response of artery contractility in aorta and in arterial pressure involving ERK activation, with an attenuation in basilarartery contractility. This action property of FTY720 would be endowed with a potential of facilitating more blood flow perfusion to the brain and improving blood supply to the ischemic brain region and could be useful as an adjuvant in the treatment of ischemic stroke in the clinics.

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“…Moreover, S1PR3-mediated Akt activation protects against in vivo myocardial ischaemia-reperfusion (Means et al, 2007). Characterization of S1PR3-deficient mice also indicates that HDL and S1P promote cardiac protection through nitric oxide/S1PR3 signaling, and exogenous S1P induces intracellular calcium increase through the S1PR3/PLC axis (Theilmeier et al, 2006; Fujii et al, 2014). …”

Section: Role For the Sphk/s1p Axis And S1pr In Cardiac Fibrosismentioning

confidence: 99%

Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis?

et al. 2017

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Sphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors, which were initially named endothelial differentiation gene (Edg) and eventually renamed sphingosine 1-phosphate receptors (S1PRs). Among the five S1PR subtypes, S1PR1, S1PR2 and S1PR3 isoforms show broad tissue gene expression, while S1PR4 is primarily expressed in immune system cells, and S1PR5 is expressed in the central nervous system. There is accumulating evidence for the important role of S1P as a mediator of many processes, such as angiogenesis, carcinogenesis and immunity, and, ultimately, fibrosis. After a tissue injury, the imbalance between the production of extracellular matrix (ECM) and its degradation, which occurs due to chronic inflammatory conditions, leads to an accumulation of ECM and, consequential, organ dysfunction. In these pathological conditions, many factors have been described to act as pro- and anti-fibrotic agents, including S1P. This bioactive lipid exhibits both pro- and anti-fibrotic effects, depending on its site of action. In this review, after a brief description of sphingolipid metabolism and signaling, we emphasize the involvement of the S1P/S1PR axis and the downstream signaling pathways in the development of fibrosis. The current knowledge of the therapeutic potential of S1PR subtype modulators in the treatment of the cardiac functions and fibrinogenesis are also examined.

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Sphingosine 1-phosphate increases an intracellular Ca2+ concentration via S1P3 receptor in cultured vascular smooth muscle cells

Cited by 15 publications

References 37 publications

Chemerin-induced arterial contraction is Gi- and calcium-dependent

Chemerin-induced arterial contraction is Gi- and calcium-dependent

FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation

Sphingosine 1-Phosphate Receptors: Do They Have a Therapeutic Potential in Cardiac Fibrosis?

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