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Published on: March 28, 2014
GABA(B) auto- versus hetero-receptor sensitivity: implications for novel pharmacotherapy
B Yu1, K Yamada, J P Gallagher
1Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
The GABA(B) agonist CGP44533 is less effective at inhibiting glutamate release than GABA release. This suggests different sensitivities of GABA and glutamate neurons to this drug.
Area of Science:
- Neuroscience
- Pharmacology
- Neurotransmission
Background:
- GABA(B) receptors are G-protein coupled receptors that modulate neurotransmitter release.
- GABA(B) receptors are found both pre-synaptically (autoreceptors and heteroreceptors) and post-synaptically.
- Differential roles of GABA(B) autoreceptors and heteroreceptors in modulating neurotransmission are not fully understood.
Purpose of the Study:
- To investigate the differential efficacy and potency of the GABA(B) agonist CGP44533 at GABA(B) autoreceptors versus heteroreceptors.
- To determine the effect of CGP44533 on GABA(A)-mediated and glutamate-mediated neurotransmission.
Main Methods:
- Uncoupling of G-protein dependent post-synaptic GABA(B) receptors.
- Application of GABA(B) agonist CGP44533 at varying concentrations (1 and 10 microM).
- Measurement of monosynaptic GABA(A)-mediated and glutamate-mediated transmission.
Main Results:
- CGP44533 showed less efficacy and potency at GABA(B) autoreceptors compared to heteroreceptors.
- 1 microM CGP44533 depressed GABA(A)-mediated transmission by 2% and glutamate transmission by 41%.
- 10 microM CGP44533 depressed GABA(A)-mediated transmission by 35% and glutamate transmission by 78%.
Conclusions:
- CGP44533 exhibits differential pharmacological sensitivity at glutamate versus GABA releasing neurons.
- Post-synaptic GABA(B) receptors play a significant role in modulating neurotransmission.
- These findings highlight the distinct roles of GABA(B) receptor subtypes in regulating neuronal excitability.
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