title: Endogenous sphingosine 1-phosphate regulates spontaneous glutamate release from mossy fiber terminals via S1P(3) receptors.
abstract: OBJECTIVE
  Previous studies have shown that sphingosine 1-phosphate (S1P) stimulates glutamate release from hippocampal neurons. The present study was designed to understand the mechanism underlying S1P-induced spontaneous glutamate release from mossy fiber terminals in the hippocampus.
  
  
  METHODS
  Slice patches were made from three different regions of neurons in rat hippocampal slices, and spontaneous α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor-mediated miniature excitatory postsynaptic currents (AMPA-mEPSCs) were monitored.
  
  
  RESULTS
  Inhibitors of sphingosine kinase such as dimethylsphingosine (DMS) and 2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole (HACPT), to suppress endogenous S1P production, significantly decreased the rate of spontaneous AMPA-mEPSCs elicited from CA3 pyramidal neurons, but not CA1 pyramidal neurons or dentate granular neurons. A similar decrease was also obtained with VPC23019, an inhibitor of S1P receptors, suramin, an inhibitor of S1P(3) receptor, U73122, an inhibitor of phospholipase C, or GF109203X, an inhibitor of protein kinase C.
  
  
  CONCLUSIONS
  The results of the present study show that endogenous S1P regulates spontaneous glutamate release in a restricted hippocampal area, i.e., the release from mossy fiber terminals, via S1P(3) receptors linked to G(q) protein. This may represent fresh insight into the regulatory mechanism of spontaneous transmitter release.
authors.affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan. tomoyuki@hyo-med.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D049349:Receptors, Lysosphingolipid / Q000187:drug effects* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
chemical_list: C525025:4-(4-(4-chloro-phenyl)thiazol-2-ylamino)phenol; D004791:Enzyme Inhibitors; D004963:Estrenes; D007211:Indoles; D008246:Lysophospholipids; D008301:Maleimides; D011760:Pyrrolidinones; D049349:Receptors, Lysosphingolipid; D013844:Thiazoles; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C060506:sphingosine 1-phosphate; D018698:Glutamic Acid; D013498:Suramin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C070515:bisindolylmaleimide I; C061800:N,N-dimethylsphingosine; D013110:Sphingosine