title: Furthering pharmacological and physiological assessment of the glutamatergic receptors at the Drosophila neuromuscular junction.
abstract: Drosophila melanogaster larval neuromuscular junctions (NMJs) serve as a model for synaptic physiology. The molecular sequences of the postsynaptic glutamate receptors have been described; however, the pharmacological profile has not been fully elucidated. The postsynaptic molecular sequence suggests a novel glutamate receptor subtype. 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 kainate/AMPA receptor agonist, blocks the postsynaptic receptors without depolarizing the muscle. However, SYM 2081, a kainate receptor agonist, did depolarize the muscle and reduce the EPSP amplitude at 1 mM but not at 0.1 mM. This supports the notion that these are generally a quisqualate subtype receptors with some oddities in the pharmacological profile. 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. This study aids in furthering the pharmokinetic profiling and specificity of the receptor subtypes.
authors.affiliation: Department of Biology, University of Kentucky, Lexington, KY, USA 40506-0225, USA.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Bhatt
authors.forename: D
authors.initials: D
authors.lastname: Bhatt
authors.forename: W-Y
authors.initials: WY
authors.lastname: Chung
authors.forename: R L
authors.initials: RL
authors.lastname: Cooper
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004330:Drosophila / Q000502:physiology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology / Q000502:physiology; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007814:Larva / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000819:agonists; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000819:agonists
chemical_list: D001569:Benzodiazepines; D003515:Cycloleucine; D005971:Glutamates; D007608:Kainic Acid; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C061950:GYKI 52466; C036361:1-amino-1,3-dicarboxycyclopentane; C046105:4-methylglutamic acid; C012301:domoic acid