Vascular sphingosine-1-phosphate S1P1 and S1P3 receptors.

摘要: The sphingolipid sphingosine-1-phosphate (S1P) acts on five subtypes of G-protein- coupled receptors, termed S1P(1) (formerly endothelial differentiation gene-1 [Edg-1]), S1P(2) (Edg-5), S1P(3) (Edg-3), S1P(4) (Edg-6) and S1P(5) (Edg-8), possibly several other "orphan" such as GPR3, GPR6 GPR12. These receptors are to different intracellular second messenger systems, including adenylate cyclase, phospholipase C, phosphatidylinositol 3-kinase/protein kinase Akt, mitogen-activated protein kinases, well Rho- Ras-dependent pathways. Consistently with this receptor multiplicity pleiotropic signaling mechanisms, S1P influences numerous cell functions. S1P(1)1, the major in cardiovascular system, where they mediate effects released from platelets, tissues (such brain). Thus enhance vascular smooth muscle proliferation migration, playing a key role developmental pathological angiogenesis. In contrast, inhibit migration these types, probably because their unique stimulatory effect GTPase-activating inhibiting activity Rac. can also cause relaxation constriction blood vessels. former is mediated by pertussis toxin-sensitive (possibly S1P(1)) located endothelium stimulating 3-kinase/Akt/endothelial nitric oxide synthase (eNOS). vasoconstricting likely be and/or via Rho-Rho-kinase, more potent coronary cerebral Finally, protects cells apoptosis through activation 3-kinase/Akt/eNOS receptors. variety effects, taken together existence multiple subtypes, provides an abundance therapeutic targets that currently still await development selective agents.