Bilirubin does not modulate ionotropic glutamate receptors or glutamate transporters

Bilirubin, a product of haemoglobin metabolism, has been suggested to damag e 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 ja undice [7]. Bilirubin is also generated in the brain following synthesis of the messenger carbon monoxide (CO) by haem oxygenase, and haem oxygenase i s upregulated in Alzheimer's disease [23]. We examined the effect of biliru bin on currents generated by NMDA and alpha -amino-3-hydroxy-5-methyl-4-iso xazole propionate (AMPA) receptors in hippocampal pyramidal cells, and on g lutamate transporter currents in retinal glial cells. Bilirubin did not mod ulate either receptor-gated currents or transporter currents. These data sh ow the negative, but important result that bilirubin does not induce neuron al death by acting directly on NMDA or AMPA receptors, nor indirectly by bl ocking glutamate uptake and raising the extracellular concentration of glut amate. (C) 2000 Elsevier Science B.V. All rights reserved.