Sphingosine-1-phosphate and modulation of vascular tone

Abstract

Sphingosine-1-phosphate (S1P) is a phosphorylated product of sphingosine, the core structure of the class of lipids termed sphingolipids. S1P is a naturally occurring lipid metabolite, and usually is present at a concentration of a few 100 nanomolar in human sera. S1P has been found to exert a diverse set of physiological and pathophysiological responses in mammalian tissues through the activation of heterotrimeric G-proteins that in turn modulate the activity of various downstream effecter molecules. In blood vessels, vascular endothelial cells and smooth muscle cells express specific receptors for S1P that modulate vascular tone. This article will provide a brief overview of S1P metabolism in the vasculature and will discuss some of the pathways whereby S1P regulates intracellular signal transduction pathways in endothelial and smooth muscle cells, leading to the activation of both vasorelaxation and vasoconstriction responses.

Sphingosine‐1‐phosphate signaling in physiology and diseases

“…NO diffuses into the underlying smooth muscle to induce relaxation through generating cyclic GMP. This S1P action is mediated via S1P 1 and S1P 3 , which activate Akt through PI 3-kinase to phosphorylate eNOS [47]. S1P 1 and S1P 3 also activate PLC to mobilize Ca 2+ , which fully activates eNOS in concert with Akt-mediated phosphorylation.…”

Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

“…1,2 Growing evidence indicates that S1P plays an important role in regulating vascular reactivity. [3][4][5] S1P is a bioactive sphingolipid metabolite and is released from erythrocytes, platelets, and endothelial cells. 6,7 The majority of S1P effects are mediated via five distinct receptors (S1P1-S1P5 receptors), which represent a family of small G proteincoupled receptors (GPCRs) 5 ; however, S1P can also exist in the cytoplasm as a second messenger involved in Ca 2+ mobilization or cell survival and proliferation.…”

“…8,9 S1P1-S1P3 receptors are expressed by a wide variety of tissues, whereas S1P4 and S1P5 receptors are mainly expressed in cells of the immune and nervous systems. 4,10 In the vasculature, endothelial cells mainly express S1P1 and S1P3 with variable expression of S1P2, whereas vascular smooth muscle cells express S1P2 and S1P3 with variable expression of S1P1. [3][4][5] Studies in animals show that application of exogenous S1P causes either vasoconstriction or vasodilation of isolated arteries from several vascular beds.…”

“…4,10 In the vasculature, endothelial cells mainly express S1P1 and S1P3 with variable expression of S1P2, whereas vascular smooth muscle cells express S1P2 and S1P3 with variable expression of S1P1. [3][4][5] Studies in animals show that application of exogenous S1P causes either vasoconstriction or vasodilation of isolated arteries from several vascular beds. 3,4 Although S1P receptor expression is detected in kidneys, [11][12][13] little is known about the effects of S1P on renal microvascular function.…”

“…[3][4][5] Studies in animals show that application of exogenous S1P causes either vasoconstriction or vasodilation of isolated arteries from several vascular beds. 3,4 Although S1P receptor expression is detected in kidneys, [11][12][13] little is known about the effects of S1P on renal microvascular function. Early studies showed that S1P evoked vasoconstriction in isolated intrarenal arteries.…”