Abstract
omega-Conotoxin MVIIA (omega-CTX MVIIA) is a reversible and potent antagonist of N-type voltage-dependent calcium channels (VDCCs) in neurons. In this study, we evaluated the effect of a fusion form of omega-CTX MVIIA with glutathione S-transferase (GST) on amygdaloid kindled seizures. Intracerebraventricular (i.c.v.) injection of the fusion protein of GST-omega-CTX MVIIA significantly decreased seizure stage and shortened afterdischarge duration and generalized seizure duration in a dose-dependent and time-related manner. In addition, GST-omega-CTX MVIIA significantly increased the GABA levels in the cortex and glycine levels in the brainstem. In contrast, GST alone did not have any effect on seizure behavior or neurochemical levels. These findings firstly demonstrate that the N-type VDCC is a potential therapeutic target for temporal lobe epilepsy. The mechanism of the anticonvulsant function of omega-CTX MVIIA is related to the blockade of N-type VDCC-mediated neurotransmitter release in the brain.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amygdala / drug effects*
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Amygdala / metabolism
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Amygdala / physiopathology
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Animals
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Anticonvulsants / pharmacology
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Brain Stem / drug effects
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Brain Stem / metabolism
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Calcium Channel Blockers / pharmacology
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Calcium Channels, N-Type / drug effects
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Calcium Channels, N-Type / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Dose-Response Relationship, Drug
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Epilepsy / drug therapy*
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Epilepsy / metabolism
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Epilepsy / physiopathology
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Epilepsy, Temporal Lobe / drug therapy
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Epilepsy, Temporal Lobe / metabolism
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Epilepsy, Temporal Lobe / physiopathology
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Glutathione Transferase / drug effects
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Glutathione Transferase / metabolism
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Glycine / metabolism
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Kindling, Neurologic / drug effects*
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Kindling, Neurologic / physiology
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Male
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Neurons / drug effects
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Neurons / metabolism
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Rats
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Rats, Sprague-Dawley
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Time Factors
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gamma-Aminobutyric Acid / metabolism
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omega-Conotoxins / pharmacology*
Substances
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Anticonvulsants
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Calcium Channel Blockers
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Calcium Channels, N-Type
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omega-Conotoxins
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gamma-Aminobutyric Acid
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ziconotide
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Glutathione Transferase
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Glycine