GLUTAMATE TANSPORTERS EXPRESSION IN THE RAT HIPPOCAMPUS AFTER Y1 OR Y2 RECEPTOR ANTAGONIST INJECTION
Abstract number :
2.021
Submission category :
Year :
2002
Submission ID :
464
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Taku Doi, Thomas C. Westfall, James L. Willmore, Yuto Ueda, Alice Gardner, Mark M. Knuepfer, Chun L. Yang, Linda Naes. Psychiatry, Miyazaki Medical College, Miyazaki, Miyazaki, Japan; Pharmacological and Physiological Science, St. Louis University, St. Lo
RATIONALE: Recently, NPY has become the focus of much attention for its possible involvement in epilepsy. Selective Y1 antagonist, administered intrahippocampally, had an anticonvulsant effect in rats. Excitatory glutamatergic neurotransmission affects the regulation of expression of NPY. On the other hand NPY suppresses glutamate release by activating Y2 receptors. We administered Y1 or Y2 antagonists to the lateral ventricle and measured the glutamate transporters (GLAST, GLT1 and EAAC1) in the rat hippocampus. The purpose was to determine if Y1 or Y2 antagonists affect expression of glutamate transporters.
METHODS: Experimental animals, Sprague Dawley rats, were injected into the lateral ventricle with BIBO3304TF (Y1 antagonist) (10-6 M) 5 [mu]l or BIIE0246TF (Y2 antagonist) (10-6 M) 5[mu]l. Control rats were injected with an equal volume of 0.9% NaCl The animals were killed at designated times, either at 2 hrs, 4 hrs, or 24 hrs after the injection and the hippocampus were removed. We used western blots to measure levels of glutamate transporters (EAAC1, GLT1, GLAST) with each antibody.
RESULTS: We observed that GLAST was increased in the hippocampus 4 hrs after the injection of a Y2 antagonist but not a Y1 antagonist.
CONCLUSIONS: A Y2 antagonist affected expression of GLAST. Suppression of glutamate release is reduced by a Y2 antagonist in hippocampal slices in vitro. The levels of GLAST expression can be increased by activation of glutamate receptors and by co-culturing with neurons. It is possible that the Y2 antagonist increased the release of glutamate and following the activation of glutamate receptors increased the expression of GLAST. It is postulated that the increase of GLAST levels works as a compensatory mechanism during excess excitation.
[Supported by: This study was supported by NIH (to Dr. Westfall). ]