Minocycline increases phosphorylation and membrane insertion of neuronal GluR1 receptors.
The tetracycline antibiotic minocycline beneficially affects neuronal functioning and also inhibits the enzyme 5-lipoxygenase (5-LOX). We hypothesized that similar to 5-LOX inhibitors, minocycline may increase phosphorylation and membrane insertion of the glutamate receptor GluR1. The experiments were performed in primary cultures of mouse striatal neurons and in the prefrontal cortex and striatum of minocycline-treated mice. In vitro, low micromolar minocycline concentrations increased GluR1 phosphorylation at Ser845 and Ser831 and increased the surface content of GluR1. Minocycline also increased GluR1 phosphorylation in vivo. Increased GluR1 phosphorylation and minocycline treatment have been associated with antidepressant and memory-enhancing activities. Direct consequences of minocycline-increased GluR1 phosphorylation are yet to be established.
The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
Marta
M
Imbesi
Tolga
T
Uz
Radmila
R
Manev
Rajiv P
RP
Sharma
Hari
H
Manev
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D018091:Receptors, AMPA / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
D016859:Lipoxygenase Inhibitors; D008911:Minocycline; D018091:Receptors, AMPA; D012694:Serine