Functional diversity of synaptic AMPA/KA receptors from rat as revealed by subtype-specific antagonists
1Center for Physiology and Pathophysiology, University of Göttingen, Germany.
Abstract:
Subtype-specific pharmacological compounds represent important tools to identify the molecular components of synaptically activated glutamate receptors in central neurones. Here, we utilized a collection of subtype-specific antagonists and modulators to investigate the functional profile of glutamate receptors in identified synapses in thin slices of the cerebellum, hippocampus and brain stem. During whole-cell patch-clamp recordings alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate (AMPA/KA) receptor-mediated synaptic currents (EPSCs) in cerebellar Purkinje cells were (i) prolonged by 100 microM cyclothiazide, (ii) not significantly changed after preincubation in 10 microM concanavalin A, (iii) not affected by 1 microM Evans Blue or polyamine toxin analogue N-(4-hydroxyphenylpropanolyl)-spermine (NHPPS), but (iv) significantly reduced by high (> or = 100 microM) concentrations of Evans Blue. These pharmacological properties were distinct from those observed in hippocampal granule cells and brain stem interneurones and markedly different from those of recombinant glutamate receptor channels GluR1-GluR6 previously investigated in heterologous expression systems.
Related Concept Videos
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Dose-Response Relationship: Selectivity and Specificity
Adrenergic Receptors: ɑ Subtype
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline moieties. Phenoxybenzamine, with a haloalkylamine...


