Comparison of Sphingosine 1-Phosphate–Induced Intracellular Signaling Pathways in Vascular Smooth Muscles: Differential Role in Vasoconstriction

Sphingosine 1-phosphate (S1P), a lipid released from activated platelets, influences physiological processes in the cardiovascular system via activation of the endothelial differentiation gene (EDG/S1P) family of 7 transmembrane G protein–coupled receptors. In cultured vascular smooth muscle (VSM) cells, S1P signaling has been shown to stimulate proliferative responses; however, its role in vasoconstriction has not been examined. In the present study, the effects of S1P and EDG/S1P receptor expression were determined in rat VSM from cerebral artery and aorta. S1P induced constriction of cerebral artery, which was partly dependent on activation of p160ROCK (Rho-kinase). S1P also induced activation of RhoA in cerebral artery with a similar time course to contraction. In aorta, S1P did not produce a constriction or RhoA activation. In VSM myocytes from cerebral arteries, stimulation with S1P gives rise to a global increase in [Ca2+]i, initially generated via Ca2+ release from the sarcoplasmic reticulum by an inositol 1,4,5-trisphosphate–dependent pathway. In aorta VSM, a small increase in [Ca2+]i was observed after stimulation at higher concentrations of S1P. S1P induced activation of p42/p44mapk in aorta and cerebral artery VSM. Subtype-specific S1P receptor antibodies revealed that the expression of S1P3/EDG-3 and S1P2/EDG-5 receptors is 4-fold higher in cerebral artery compared with aorta. S1P1/EDG-1 receptor expression was similar in both types of VSM. Therefore, the ability of S1P to act as a vasoactive mediator is dependent on the activation of associated signaling pathways and may vary in different VSM. This differential signaling may be related to the expression of S1P receptor subtypes.

[1]  Tomio Sasaki,et al.  Sphingosine 1-Phosphate Contracts Canine Basilar Arteries In Vitro and In Vivo: Possible Role in Pathogenesis of Cerebral Vasospasm , 2001, Stroke.

[2]  T. Hla,et al.  Role of the Sphingosine 1-Phosphate Receptor EDG-1 in Vascular Smooth Muscle Cell Proliferation and Migration , 2001, Circulation research.

[3]  B. Friedman,et al.  Selective Loss of Sphingosine 1-Phosphate Signaling with No Obvious Phenotypic Abnormality in Mice Lacking Its G Protein-coupled Receptor, LPB3/EDG-3* , 2001, The Journal of Biological Chemistry.

[4]  N. Sugimoto,et al.  Rho activation in excitatory agonist-stimulated vascular smooth muscle. , 2001, American journal of physiology. Cell physiology.

[5]  T. Hla.  Sphingosine 1-phosphate receptors. , 2001, Prostaglandins & other lipid mediators.

[6]  M. Nelson,et al.  Differential regulation of Ca(2+) sparks and Ca(2+) waves by UTP in rat cerebral artery smooth muscle cells. , 2000, American journal of physiology. Cell physiology.

[7]  S. Pyne,et al.  Sphingosine 1-phosphate signalling via the endothelial differentiation gene family of G-protein-coupled receptors. , 2000, Pharmacology & therapeutics.

[8]  J. P. Hobson,et al.  Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. , 2000, The Journal of clinical investigation.

[9]  K. Jakobs,et al.  Sphingosine‐1‐phosphate reduces rat renal and mesenteric blood flow in vivo in a pertussis toxin‐sensitive manner , 2000, British journal of pharmacology.

[10]  K. Jakobs,et al.  Sphingosine‐1‐phosphate and sphingosylphosphorylcholine constrict renal and mesenteric microvessels in vitro , 2000, British journal of pharmacology.

[11]  B. O'dowd,et al.  Characterization of a Novel Sphingosine 1-Phosphate Receptor, Edg-8* , 2000, The Journal of Biological Chemistry.

[12]  S. Milstien,et al.  Functions of a new family of sphingosine-1-phosphate receptors. , 2000, Biochimica et biophysica acta.

[13]  A. Somlyo,et al.  Signal transduction by G‐proteins, Rho‐kinase and protein phosphatase to smooth muscle and non‐muscle myosin II , 2000, The Journal of physiology.

[14]  A. Barr,et al.  Differential Coupling of the Sphingosine 1-Phosphate Receptors Edg-1, Edg-3, and H218/Edg-5 to the Gi, Gq, and G12 Families of Heterotrimeric G Proteins* , 1999, The Journal of Biological Chemistry.

[15]  T. Hla,et al.  Differential Pharmacological Properties and Signal Transduction of the Sphingosine 1-Phosphate Receptors EDG-1, EDG-3, and EDG-5* , 1999, The Journal of Biological Chemistry.

[16]  K. Dobashi,et al.  Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca2+ sensitization. , 1999, American journal of respiratory cell and molecular biology.

[17]  T. Bleu,et al.  Transduction of intracellular calcium signals through G protein-mediated activation of phospholipase C by recombinant sphingosine 1-phosphate receptors. , 1999, Molecular pharmacology.

[18]  G. Nixon,et al.  Expression and distribution of the type 1 and type 3 inositol 1,4, 5-trisphosphate receptor in developing vascular smooth muscle. , 1999, Circulation research.

[19]  S. Pyne,et al.  Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle. Role of endothelial differentiation gene 1, c-Src tyrosine kinase and phosphoinositide 3-kinase. , 1999, The Biochemical journal.

[20]  S. Pyne,et al.  Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle , 1999 .

[21]  M. Ui,et al.  Activation of phospholipase C‐Ca2+ system by sphingosine 1‐phosphate in CHO cells transfected with Edg‐3, a putative lipid receptor , 1999, FEBS letters.

[22]  A. Somlyo,et al.  The effects of the Rho‐kinase inhibitor Y‐27632 on arachidonic acid‐, GTPγS‐, and phorbol ester‐induced Ca2+‐sensitization of smooth muscle , 1998, FEBS letters.

[23]  M. Lipp,et al.  EDG6, a novel G-protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue. , 1998, Genomics.

[24]  A. Gilman,et al.  p115 RhoGEF, a GTPase activating protein for Gα12 and Gα13 , 1998 .

[25]  C. H. Liu,et al.  Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. , 1998, Science.

[26]  S. Brenner,et al.  Molecular cloning of the novel human G protein-coupled receptor (GPCR) gene mapped on chromosome 9. , 1996, Biochemical and biophysical research communications.

[27]  Kozo Kaibuchi,et al.  Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase) , 1996, Science.

[28]  T. Hla,et al.  The Inducible G Protein-coupled Receptor edg-1 Signals via the G/Mitogen-activated Protein Kinase Pathway (*) , 1996, The Journal of Biological Chemistry.

[29]  S. Hakomori,et al.  Sphingosine-1-phosphate: a platelet-activating sphingolipid released from agonist-stimulated human platelets. , 1995, Blood.

[30]  S. Spiegel,et al.  Sphingosine 1-phosphate rapidly activates the mitogen-activated protein kinase pathway by a G protein-dependent mechanism , 1995, The Journal of Biological Chemistry.

[31]  S. Spiegel,et al.  Sphingosine-1-phosphate, a putative second messenger, mobilizes calcium from internal stores via an inositol trisphosphate-independent pathway. , 1994, The Journal of biological chemistry.

[32]  N. Ishizaka,et al.  Molecular cloning of a novel putative G protein-coupled receptor expressed in the cardiovascular system. , 1993, Biochemical and biophysical research communications.

[33]  M. Nelson,et al.  Regulation of arterial tone by activation of calcium-dependent potassium channels. , 1992, Science.

[34]  T. Hla,et al.  An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors. , 1990, The Journal of biological chemistry.

[35]  T. Kanda,et al.  Extracellular mechanism through the Edg family of receptors might be responsible for sphingosine-1-phosphate-induced regulation of DNA synthesis and migration of rat aortic smooth-muscle cells. , 2001, The Biochemical journal.

[36]  T. Kanda,et al.  Extracellular mechanism through the Edg family of receptors might be responsible for sphingosine-1-phosphate-induced regulation of DNA synthesis and migration of rat aortic smooth-muscle cells , 2000 .