Bilirubin does not modulate ionotropic glutamate receptors or glutamate transporters.
Bilirubin, a product of haemoglobin metabolism, has been suggested to damage neurons by increasing activation of N-methyl-D-aspartate (NMDA) receptors when it reaches high levels in the blood [15,19], as occurs in neonatal jaundice [7]. Bilirubin is also generated in the brain following synthesis of the messenger carbon monoxide (CO) by haem oxygenase, and haem oxygenase is upregulated in Alzheimer's disease [23]. We examined the effect of bilirubin on currents generated by NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors in hippocampal pyramidal cells, and on glutamate transporter currents in retinal glial cells. Bilirubin did not modulate either receptor-gated currents or transporter currents. These data show the negative, but important result that bilirubin does not induce neuronal death by acting directly on NMDA or AMPA receptors, nor indirectly by blocking glutamate uptake and raising the extracellular concentration of glutamate.
Warr
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Department of Physiology, University College London, Gower Street, WC1E 6BT, London, UK.
Mort
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Attwell
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D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000502:physiology*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001663:Bilirubin