GLUTAMATE-RECEPTOR SUBTYPE EXPRESSION IN HUMAN POSTMORTEM BRAIN

Antibodies to functional glutamate receptor subunits were utilized as probes to characterize glutamatergic receptors in human postmortem bra in tissue. Crude membranes from rat, monkey, and various dissected hum an postmortem brain regions were fractionated by SDS-PAGE and electrot ransferred to nitrocellulose. Using antisera raised against rat antige ns for AMPA/kainate (GluR1-3) and kainate (GluR5) glutamate receptor s ubunits, we have been able to detect specific bands on Western blots i n rat, monkey, and human postmortem brain tissue. These antisera recog nized bands at approx 105 kDa for the GluR1-3 and 115 kDa for GluR5 in humans, monkeys, and rats. All of these glutamate receptor subtypes a ppear to be glycosylated. We observed varying levels of expression in the human brain areas examined, with the highest degree of expression in the hippocampus and temporal cortex for AMPA/kainate receptor subun its, and in the cortex and cerebellum for the kainate receptor subunit s. In addition, considerable heterogeneity in expression was observed between patient samples with these antisera, as well as with antisera to the structural protein, NCAM. Our studies indicate that glutamaterg ic receptor protein changes related to various human disease states ma y be examined in human postmortem tissue by Western blotting technique s utilizing these antibodies raised to the rat protein.