Arachidonic acid and anandamide have opposite modulatory actions at the glycine transporter, GLYT1a
Article first published online: 13 JAN 2003
Journal of Neurochemistry
Volume 84, Issue 3, pages 592–601, February 2003
How to Cite
Pearlman, R. J., Aubrey, K. R. and Vandenberg, R. J. (2003), Arachidonic acid and anandamide have opposite modulatory actions at the glycine transporter, GLYT1a. Journal of Neurochemistry, 84: 592–601. doi: 10.1046/j.1471-4159.2003.01549.x
- Issue published online: 13 JAN 2003
- Article first published online: 13 JAN 2003
- Received July 18, 2002; revised manuscript received September 23, 2002; accepted October 30, 2002.
- arachidonic acid;
- glycine transporter
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.