Pharmacological heterogeneity of release-regulating presynaptic AMPA/kainate receptors in the rat brain: study with receptor antagonists

Pharmacological heterogeneity of release-regulating presynaptic AMPA/kainate receptors in the rat... Presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptors mediating hippocampal ( 3 H)noradrenaline or ( 3 H)serotonin release, striatal ( 3 H)dopamine release and cortical ( 3 H)acetylcholine release were pharmacologically characterized using several AMPA/kainate receptor antagonists. The releases of the four transmitters elicited by exposing synaptosomes to AMPA were antagonized by NBQX, indicating that they reflect AMPA/kainate receptor activation. GYKI52466 did not inhibit the AMPA-induced release of ( 3 H)noradrenaline, ( 3 H)dopamine or ( 3 H)serotonin, while it weakly affected the AMPA-mediated release of ( 3 H)acetylcholine. On the contrary, LY300164 and LY303070 were potent antagonists able to discriminate among AMPA/kainate receptor subtypes. Both compounds blocked the AMPA receptors mediating ( 3 H)dopamine and ( 3 H)acetylcholine release. However, LY303070, but not LY300164, inhibited the AMPA-induced release of ( 3 H)noradrenaline, while the AMPA-mediated ( 3 H)serotonin release was sensitive to LY300164 but not to LY303070. SYM2206 mimicked LY300164 and prevented the AMPA-induced release of ( 3 H)dopamine, ( 3 H)acetylcholine and ( 3 H)serotonin, but not that of ( 3 H)noradrenaline. NS102 failed to antagonize the AMPA-induced release of all four transmitters. LY293558 prevented the AMPA-mediated release of ( 3 H)noradrenaline, ( 3 H)dopamine, ( 3 H)acetylcholine or ( 3 H)serotonin. Differently, LY377770 did not inhibit the AMPA-mediated release of ( 3 H)noradrenaline and ( 3 H)acetylcholine, but it potently blocked the AMPA-induced release of ( 3 H)serotonin and, less so, of ( 3 H)dopamine. AMOA inhibited the AMPA-induced release of ( 3 H)serotonin or ( 3 H)acetylcholine, but not that of ( 3 H)noradrenaline or ( 3 H)dopamine. GAMS prevented the AMPA-mediated release of ( 3 H)acetylcholine and, more weakly, that of ( 3 H)dopamine, but it failed to inhibit the release of ( 3 H)noradrenaline or ( 3 H)serotonin elicited by AMPA. γ-DGG did not affect the AMPA-mediated release of any of the four transmitters studied. In conclusion, based on the antagonist profiles obtained, the four receptors here analyzed all belong to the AMPA-preferring subclass of glutamate receptors; however, they appear to differ from each other, probably due to differences in subunit composition. The compounds LY300164, LY303070, LY377770, AMOA and GAMS may be useful to discriminate among AMPA-preferring receptor subtypes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurochemistry International Elsevier

Pharmacological heterogeneity of release-regulating presynaptic AMPA/kainate receptors in the rat brain: study with receptor antagonists

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Publisher
Elsevier
Copyright
Copyright © 2002 Elsevier Science Ltd
ISSN
0197-0186
DOI
10.1016/S0197-0186(02)00129-8
Publisher site
See Article on Publisher Site

Abstract

Presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptors mediating hippocampal ( 3 H)noradrenaline or ( 3 H)serotonin release, striatal ( 3 H)dopamine release and cortical ( 3 H)acetylcholine release were pharmacologically characterized using several AMPA/kainate receptor antagonists. The releases of the four transmitters elicited by exposing synaptosomes to AMPA were antagonized by NBQX, indicating that they reflect AMPA/kainate receptor activation. GYKI52466 did not inhibit the AMPA-induced release of ( 3 H)noradrenaline, ( 3 H)dopamine or ( 3 H)serotonin, while it weakly affected the AMPA-mediated release of ( 3 H)acetylcholine. On the contrary, LY300164 and LY303070 were potent antagonists able to discriminate among AMPA/kainate receptor subtypes. Both compounds blocked the AMPA receptors mediating ( 3 H)dopamine and ( 3 H)acetylcholine release. However, LY303070, but not LY300164, inhibited the AMPA-induced release of ( 3 H)noradrenaline, while the AMPA-mediated ( 3 H)serotonin release was sensitive to LY300164 but not to LY303070. SYM2206 mimicked LY300164 and prevented the AMPA-induced release of ( 3 H)dopamine, ( 3 H)acetylcholine and ( 3 H)serotonin, but not that of ( 3 H)noradrenaline. NS102 failed to antagonize the AMPA-induced release of all four transmitters. LY293558 prevented the AMPA-mediated release of ( 3 H)noradrenaline, ( 3 H)dopamine, ( 3 H)acetylcholine or ( 3 H)serotonin. Differently, LY377770 did not inhibit the AMPA-mediated release of ( 3 H)noradrenaline and ( 3 H)acetylcholine, but it potently blocked the AMPA-induced release of ( 3 H)serotonin and, less so, of ( 3 H)dopamine. AMOA inhibited the AMPA-induced release of ( 3 H)serotonin or ( 3 H)acetylcholine, but not that of ( 3 H)noradrenaline or ( 3 H)dopamine. GAMS prevented the AMPA-mediated release of ( 3 H)acetylcholine and, more weakly, that of ( 3 H)dopamine, but it failed to inhibit the release of ( 3 H)noradrenaline or ( 3 H)serotonin elicited by AMPA. γ-DGG did not affect the AMPA-mediated release of any of the four transmitters studied. In conclusion, based on the antagonist profiles obtained, the four receptors here analyzed all belong to the AMPA-preferring subclass of glutamate receptors; however, they appear to differ from each other, probably due to differences in subunit composition. The compounds LY300164, LY303070, LY377770, AMOA and GAMS may be useful to discriminate among AMPA-preferring receptor subtypes.

Journal

Neurochemistry InternationalElsevier

Published: Mar 1, 2003

References

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