title: Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase.
abstract: Astrocytes play a critical role in neurovascular coupling by providing a physical linkage from synapses to arterioles and releasing vaso-active gliotransmitters. We identified a gliotransmitter pathway by which astrocytes influence arteriole lumen diameter. Astrocytes synthesize and release NMDA receptor coagonist, D-serine, in response to neurotransmitter input. Mouse cortical slice astrocyte activation by metabotropic glutamate receptors or photolysis of caged Ca(2+) produced dilation of penetrating arterioles in a manner attenuated by scavenging D-serine with D-amino acid oxidase, deleting the enzyme responsible for D-serine synthesis (serine racemase) or blocking NMDA receptor glycine coagonist sites with 5,7-dichlorokynurenic acid. We also found that dilatory responses were dramatically reduced by inhibition or elimination of endothelial nitric oxide synthase and that the vasodilatory effect of endothelial nitric oxide synthase is likely mediated by suppressing levels of the vasoconstrictor arachidonic acid metabolite, 20-hydroxy arachidonic acid. Our results provide evidence that D-serine coactivation of NMDA receptors and endothelial nitric oxide synthase is involved in astrocyte-mediated neurovascular coupling.
authors: Department of Pharmacology and Therapeutics,  University of Manitoba, Winnipeg, MB,  Canada R3E 0T6.
authors: Jillian L LeMaistre
authors: JL
authors: Stobart
authors: Lingling
authors: L
authors: Lu
authors: Hope D I
authors: HD
authors: Anderson
authors: Hisashi
authors: H
authors: Mori
authors: Christopher M
authors: CM
authors: Anderson
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology*; D001253:Astrocytes / Q000166:cytology*; D001921:Brain / Q000098:blood supply*; D015232:Dinoprostone / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012694:Serine / Q000502:physiology*; D014664:Vasodilation
chemical_list: D018094:Receptors, Metabotropic Glutamate; D012694:Serine; D052250:Nitric Oxide Synthase Type III; D015232:Dinoprostone
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