Arachidonic acid and anandamide have opposite modulatory actions at the glycine transporter, GLYT1a.
The GLYT1 subtypes of glycine transporter are expressed in glia surrounding excitatory synapses in the mammalian CNS and may regulate synaptic glycine concentrations required for activation of the NMDA subtypes of glutamate receptor. In this report we demonstrate that the rate of glycine transport by GLYT1 is inhibited by arachidonic acid. The cyclo-oxygenase and lipoxygenase inhibitors indomethacin and nordihydroguaiaretic acid, and the protein kinase C inhibitor staurosporine, had no effect on the extent of arachidonic acid inhibition of transport, which suggests that the inhibitory effects of arachidonic acid result from a direct interaction with the transporter. In contrast to arachidonic acid, its amide derivative, anandamide, and the more stable analogue R1-methanandamide stimulate glycine transport. This stimulation is unlikely to be a secondary effect of cannabinoid receptor stimulation because the cannabinoid receptor agonist WIN 55 212-2 had no effect on transport. We suggest that the stimulatory effects of anandamide on GLYT1 are due to a direct interaction with the transporter.
Pearlman
Rhonda Jo
RJ
Department of Pharmacology and Institute for Biomedical Research, University of Sydney, Sydney, New South Wales, Australia.
Aubrey
Karin R
KR
Vandenberg
Robert J
RJ
D026921:Amino Acid Transport Systems, Neutral / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D063388:Endocannabinoids; D005910:Glioma / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014162:Transfection; D014982:Xenopus laevis
D026921:Amino Acid Transport Systems, Neutral; D001095:Arachidonic Acids; D063388:Endocannabinoids; D050487:Glycine Plasma Membrane Transport Proteins; D053284:Polyunsaturated Alkamides; D020033:Protein Isoforms; C493266:Slc6a9 protein, rat; C088155:methanandamide; D016718:Arachidonic Acid; D005998:Glycine; C078814:anandamide