A novel physiological mechanism of glycine-induced immunomodulation: Na+-coupled amino acid transporter currents in cultured brain macrophages.
Glycine is known to modulate immune cell responses. However, the physiological mechanisms underlying inhibitory effects of glycine on macrophages are not well understood. Here we show that glycine is capable of inducing inward currents in brain macrophages (microglia). In contrast to glycine, the glycine receptor agonist taurine failed to elicit currents. Glycine-evoked currents of brain macrophages were unaffected by strychnine, Cl(-)-free extracellular solution, N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl])sarcosine (NFPS) and amoxapine, but were abolished upon omission of extracellular Na(+). Furthermore, glycine caused increases in the intracellular Na(+) concentration and pronounced membrane depolarization. Glycine-evoked depolarization was Na(+) dependent and occurred independently of the intracellular Cl(-) concentration. Similarly to glycine, glutamine and alpha-(methylamino)isobutyric acid (MeAIB) elicited inward currents in brain macrophages. In the presence of either glutamine or MeAIB, glycine-induced currents were inhibited. It is concluded that neither functional glycine receptors nor glycine transporters are expressed in brain macrophages. We suggest that glycine mediates its effects by activation of system A Na(+)-coupled neutral amino acid transporters.
Schilling
Tom
T
Institute of Physiology, Humboldt University, Tucholsky Str. 2, D-10117 Berlin, Germany.
Eder
Claudia
C
D026921:Amino Acid Transport Systems, Neutral / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000502:physiology*; D050487:Glycine Plasma Membrane Transport Proteins; D007155:Immunologic Factors / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice
D026921:Amino Acid Transport Systems, Neutral; D050487:Glycine Plasma Membrane Transport Proteins; D007155:Immunologic Factors; D005998:Glycine