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FURTHERING PHARMACOLOGICAL AND PHYSIOLOGICAL ASSESSMENT OF THE GLUTAMATERGIC RECEPTORS AT THE DROSOPHILA NEUROMUSCULAR JUNCTIONLee, Junyoung 01 January 2009 (has links)
Drosophila larval neuromuscular junctions (NMJs) serve as a model for synaptic physiology. The molecular sequence of the postsynaptic glutamate receptors has been described; however, the pharmacological profile has not been fully elucidated. Despite the postsynaptic molecular sequence used to classify the receptors as a kainate subtype, they do not respond pharmacologically as such. Kainate does not depolarize the muscle, but dampens evoked EPSP amplitudes. Quantal responses show a decreased amplitude and area under the voltage curve indicative of reduced postsynaptic receptor sensitivity to glutamate transmission. ATPA, a kainate receptor agonist, did not mimic kainate’s action. The metabotropic glutamate receptor agonist t-ACPD had no effect. Domoic acid, a quisqualate receptor antagonist, blocks the postsynaptic receptors without depolarizing the muscle, which supports the presence of quisqualate subtype receptors. The results suggest a direct postsynaptic action of kainate due to partial antagonist action on the quisqualate receptors. There does not appear to be presynaptic auto-regulation via a kainate receptor subtype or a metabotropic auto-receptor. A complete pharmacological profiling of the known receptor subtypes at this NMJ has not yet occurred; however, this study aids in furthering the ongoing investigations to provide a clearer picture of pharmokinetic profile and specificity of the receptor subtypes.
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