Identification of eugenol as the major determinant of GABAA-receptor activation by aqueous Syzygium aromaticum L. (clove buds) extract

2017 ◽  
Vol 37 ◽  
pp. 641-649 ◽  
Author(s):  
Sümeyye Sahin ◽  
Volker Eulenburg ◽  
Anja Heinlein ◽  
Carmen Villmann ◽  
Monika Pischetsrieder
Keyword(s):  
Gabaa Receptor ◽  
Receptor Activation ◽  
Major Determinant ◽  
Syzygium Aromaticum

GABAA receptor activation and open-channel block by volatile anaesthetics: a new principle of receptor modulation?

2002 ◽  
Vol 451 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Rainer Haseneder ◽  
Gerhard Rammes ◽  
Walter Zieglgänsberger ◽  
Eberhard Kochs ◽  
Gerhard Hapfelmeier
Keyword(s):  
Gabaa Receptor ◽  
Open Channel ◽  
Receptor Activation ◽  
Channel Block ◽  
Volatile Anaesthetics ◽  
Open Channel Block ◽  
Receptor Modulation

scholarly journals Analysis of GABAA Receptor Activation by Combinations of Agonists Acting at the Same or Distinct Binding Sites

2018 ◽  
Vol 95 (1) ◽  
pp. 70-81 ◽  
Author(s):  
Daniel J. Shin ◽  
Allison L. Germann ◽  
Douglas F. Covey ◽  
Joe Henry Steinbach ◽  
Gustav Akk
Keyword(s):  
Gabaa Receptor ◽  
Binding Sites ◽  
Receptor Activation

In vitro and in vivo GABAA Receptor Interaction of the Propanidid Metabolite 4-(2-[Diethylamino]-2-Oxoethoxy)-3-Methoxy-Benzeneacetic Acid

Pharmacology ◽  
2018 ◽  
Vol 103 (1-2) ◽  
pp. 10-16 ◽  
Author(s):  
Alessia Cenani ◽  
Robert J. Brosnan ◽  
Heather K. Knych
Keyword(s):  
Gabaa Receptor ◽  
Gabaa Receptors ◽  
Water Solubility ◽  
Plasma Concentrations ◽  
Receptor Activation ◽  
Receptor Interaction ◽  
Dependent Manner ◽  
Benzeneacetic Acid

Background: Propanidid is a γ-aminobutyric acid type A (GABAA) receptor agonist general anesthetic and its primary metabolite is 4-(2-[diethylamino]-2-oxoethoxy)-3-methoxy-benzeneacetic acid (DOMBA). Despite having a high water solubility at physiologic pH that might predict low-affinity GABAA receptor interactions, DOMBA is reported to have no effect on GABAA receptor currents, possibly because the DOMBA concentrations studied were simply insufficient to modulate GABAA receptors. Our objectives were to measure the propanidid and DOMBA concentration responses on ­GABAA receptors and to measure the behavioral responses of DOMBA in mice at concentrations that affect GABAA receptor currents in vitro. Methods: GABAA receptors were expressed in oocytes using clones for the human GABAA α1, β2 and γ2s subunits. The effects of DOMBA (0.2–10 mmol/L) and propanidid (0.001–1 mmol/L) on oocyte GABAA currents were studied using standard 2-electrode voltage clamp techniques. Based on in vitro results, 6 mice received ­DOMBA 32 mg intraperitoneal and were observed for occurrence of neurologic effects and DOMBA plasma concentration was measured by liquid chromatography tandem mass spectrometry. Results: DOMBA both directly activates GABAA receptors and antagonizes its GABA-mediated opening in a concentration-dependent manner at concentrations between 5–10 and 0.5–10 mmol/L respectively. In vivo, DOMBA produced rapid onset sedation at plasma concentrations that correlate with direct GABAA receptor activation. Conclusion: DOMBA modulation of GABAA receptors is associated with sedation in mice. Metabolites of propanidid analogues currently in development may similarly modulate GABAA, and impaired elimination of these metabolites could produce clinically relevant neurophysiologic effects.

scholarly journals Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex

2014 ◽  
Vol 8 ◽  
Author(s):  
Tomonori Furukawa ◽  
Junko Yamada ◽  
Tenpei Akita ◽  
Yoshitaka Matsushima ◽  
Yuchio Yanagawa ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Gabaa Receptor ◽  
Receptor Activation ◽  
Radial Migration ◽  
Fetal Mouse ◽  
Mouse Cerebral Cortex

Spontaneous GABAA receptor-mediated inhibitory currents in adult rat somatosensory cortex

1996 ◽  
Vol 75 (4) ◽  
pp. 1573-1588 ◽  
Author(s):  
P. A. Salin ◽  
D. A. Prince
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Decay Time ◽  
High Frequency ◽  
Pyramidal Cells ◽  
Receptor Activation ◽  
Inhibitory Interneurons ◽  
Adult Rat ◽  
Bath Application

1. Spontaneous inhibitory synaptic currents (sIPSCs) were studied with whole cell voltage-clamp recordings from 131 pyramidal cells in adult rat somatosensory cortical slices. Neurons were intracellulary labeled with biocytin and classified as supragranular (SG, layers 2-3), layer IV (IV), or infragranular (IG, layer V) on the basis of the laminar localization of their somata. Somatic areas were similar for SG, IV, and IG neurons. All identified pyramidal cells generated high-frequency gamma-aminobutyric acid (GABAA) receptor-mediated synaptic events. 2. Bath application of bicuculline blocked the sIPSCs and resulted in a decrease of approximately 0.5 nS in resting conductance and an inward shift in baseline current. 3. sIPSC frequency was significantly lower in SG versus IG or IV neurons, and this difference was accounted for by the occurrence of a higher percentage of bursts of sIPSCs in the IG and IV neurons. 4. Bath application of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) decreased the frequency of sIPSCs by 13-21%. By contrast, application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-AP5) generally had no effect on spontaneous IPSC frequency, suggesting that AMPA rather than NMDA receptor activation contributed to resting discharge of inhibitory interneurons. 5. Addition of tetrodotoxin (TTX) to the perfusion medium reduced the spontaneous IPSC frequency by approximately 30-55%. The miniature IPSCs (mIPSCs) seen in TTX-containing solutions had a frequency of approximately 10 Hz and an average conductance of 0.42-0.48 nS. 6. The kinetic properties of mIPSCs generated in pyramidal cells of different layers were the same, with the rise times of approximately 0.9 ms and decay time constants of approximately 8 ms at a holding potential of 0 mV. The decay phase of mIPSCs was generally fitted by one exponential and displayed a voltage dependence with an e-fold increase in decay time constant for a every 198-mV depolarization. 7. These results show that there is ongoing spontaneous release of GABA in neocortical slices that gives rise to high-frequency impulse-related and non-impulse-related postsynaptic inhibitory currents. Activation of AMPA receptors on inhibitory interneurons accounts for only a small proportion of the GABAA receptor-mediated events. Judging from the distribution of mIPSC frequencies in neurons of different laminae, there is a relatively uniform distribution of inhibitory synapses throughout the cortex. Tonic activation of GABAA receptors on neocortical pyramidal neurons generates an increase in resting membrane conductance that may play an important role in vivo by preventing the development of hyperexcitability, modulating excitatory synaptic events, and controlling the rate and patterns of spike discharge.

Peripheral GABAA receptor activation modulates rat tongue afferent mechanical sensitivity

2014 ◽  
Vol 59 (3) ◽  
pp. 251-257 ◽  
Author(s):  
Sun Nee Tan ◽  
Esther Song ◽  
Xu-Dong Dong ◽  
Rishi Kumar Somvanshi ◽  
Brian E. Cairns
Keyword(s):  
Gabaa Receptor ◽  
Receptor Activation ◽  
Mechanical Sensitivity ◽  
Rat Tongue
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