AMPA (AMINO-3-HYDROXY-5-METHYLISOXAZOLE-4-PROPIONIC ACID) RECEPTORS IN HUMAN BRAIN-TISSUES

AMPA receptors may play an important role in acute and chronic neurode generative diseases. An assay for the specific binding of H-3]-amino-3 -hydroxy-5-methylisoxazole-4-propionic acid (AMPA) to receptors in mem branes from post-mortem human brain is described, which can be used in screening for selective AMPA receptor antagonists. Membranes were pre pared from frozen human adult hippocampus and whole fetal brain tissue s. [H-3]-AMPA binding to human hippocampus was saturable; Scatchard an alysis of equilibrium binding data indicated high and low affinity sit es with affinity binding constants (K-D) of 3.4 +/- 0.5 nM and 65 +/- 9 nM (n=7) respectively. Biphasic association and dissociation rate co nstants for [H-3]-AMPA binding were consistent with the biphasic Scatc hard analysis. Inhibition of [H-3]-AMPA binding revealed a rank order of potency as quisqualate = AMPA > BOAA > L-glutamate DNQX = CNQX > ka inate > L-aspartate = NMDA. AMPA receptors in human fetal brain had a comparable pharmacology. AMPA/kainate receptors were expressed in frog oocytes following injection of RNA prepared from human fetal brain. H uman brain tissues may therefore be utilized for screening and functio nal analysis of AMPA receptor antagonists.