Modulation of GABA-Gated Chloride Ion Influx in the Brain by Dehydroepiandrosterone and Its Metabolites

1998 ◽  
Vol 243 (3) ◽  
pp. 771-775 ◽  
Author(s):  
Makoto Imamura ◽  
Chandan Prasad
Keyword(s):  
Chloride Ion ◽  
Chloride Ion Influx ◽  
Ion Influx ◽  
The Brain

GABA-gated chloride ion influx and receptor binding studies in C57BL6J and DBA2J mice

1986 ◽  
Vol 399 (2) ◽  
pp. 374-378 ◽  
Author(s):  
Onnfoh Yu ◽  
Masatoshi Ito ◽  
Ted H. Chiu ◽  
Howard C. Rosenberg
Keyword(s):  
Receptor Binding ◽  
Chloride Ion ◽  
Binding Studies ◽  
Chloride Ion Influx ◽  
Ion Influx

A Pertussis Toxin-Sensitive 8-Lipoxygenase Pathway Is Activated by a Nicotinic Acetylcholine Receptor inAplysia Neurons

2001 ◽  
Vol 85 (5) ◽  
pp. 2150-2158 ◽  
Author(s):  
Tamara L. Tieman ◽  
Douglas J. Steel ◽  
Yelena Gor ◽  
Jacsue Kehoe ◽  
James H. Schwartz ◽  
...  
Keyword(s):  
Pertussis Toxin ◽  
Chloride Ion ◽  
Chloride Ions ◽  
Chloride Conductance ◽  
Lipoxygenase Pathway ◽  
Aplysia Neurons ◽  
Chloride Ion Influx ◽  
Electrophysiological Responses ◽  
Ion Influx ◽  
Lipid Metabolites

Acetylcholine (ACh) activates two types of chloride conductances in Aplysia neurons that can be distinguished by their kinetics and pharmacology. One is a rapidly desensitizing current that is blocked by α-conotoxin-ImI and the other is a sustained current that is insensitive to the toxin. These currents are differentially expressed in Aplysia neurons. We report here that neurons that respond to ACh with a sustained chloride conductance also generate 8-lipoxygenase metabolites. The sustained chloride conductance and the activation of 8-lipoxygenase have similar pharmacological profiles. Both are stimulated by suberyldicholine and nicotine, and both are inhibited by α-bungarotoxin. Like the sustained chloride conductance, the activation of 8-lipoxygenase is not blocked by α-conotoxin-ImI. In spite of the similarities between the metabolic and electrophysiological responses, the generation of 8-lipoxygenase metabolites does not appear to depend on the ion current since an influx of chloride ions is neither necessary nor sufficient for the formation of the lipid metabolites. In addition, the application of pertussis toxin blocked the ACh-activated release of arachidonic acid and the subsequent production of 8-lipoxygenase metabolites, yet the ACh-induced activation of the chloride conductance is not dependent on a G protein. Our results are consistent with the idea that the nicotinic ACh receptor that activates the sustained chloride conductance can, independent of the chloride ion influx, initiate lipid messenger synthesis.

Synthesis and Evaluation of α-Asaronol Esters with LDH and GABAA Receptor Modulation as Anticonvulsant Agents

2020 ◽  
Vol 17 (7) ◽  
pp. 891-904
Author(s):  
Yajun Bai ◽  
Bin Li ◽  
Jing Xie ◽  
Xufei Chen ◽  
Shu Cheng ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Chloride Ion ◽  
Neuroprotective Effects ◽  
Receptor Modulation ◽  
Chloride Ion Influx ◽  
Weak Activity ◽  
Ion Influx ◽  
Low Toxicity ◽  
Derivatives Of

Background: Our previous studies showed that α-asaronol was a potential antiepileptic candidate. Here, twelve O-terminus modified ester derivatives of α-asaronol were designed, synthesized and evaluated their anticonvulsant activity. Methods: All synthetic compounds were subjected to three animal models of seizure (MES, scPTZ and sc3-MP models) combined with neurotoxicity test, as well as the LDH inhibitory test. Furthermore, GABAA Receptor modulation and pharmacokinetic evaluation of compound 4k were also performed. Results: Five compounds (4a, 4b, 4d, 4e and 4k) showed significant anticonvulsant properties at the dose of 30-300 mg/kg in MES and scPTZ test, but weak activity in sc3-MP model. Meanwhile, 4a, 4b, 4d and 4k showed good LDH inhibitory activity in vitro. Specifically, 4k was the best compound in above evaluation, and better than that of α-asaronol and reference compound (stiripentol). In addition, 4k could increase chloride ion influx by modulating GABAA receptor α1β2γ2 subtype with EC50 of 48.65 ± 10.31 μM and showed good PK profiles in rats with moderate oral bioavailability (51.5%). Conclusion: These results suggested 4k possesses potential effectiveness in treatment of therapyresistant seizures and is expected to be developed as a novel molecule for safer and efficient anticonvulsants having neuroprotective effects as well as low toxicity.

scholarly journals Lactobacillus casei reduces susceptibility to type 2 diabetes via microbiota-mediated body chloride ion influx

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Yong Zhang ◽  
Xiao Guo ◽  
Jianlin Guo ◽  
Qiuwen He ◽  
He Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lactobacillus Casei ◽  
Chloride Ion ◽  
Chloride Ion Influx ◽  
Ion Influx

GABA-gated chloride ion influx in brains of tremor rats

1993 ◽  
Vol 18 (9) ◽  
pp. 977-981 ◽  
Author(s):  
Kazuko Kishi ◽  
Masatoshi Ito ◽  
Akemi Tsuda ◽  
Hideo Tsuda ◽  
Hideyuki Shiraishi ◽  
...  
Keyword(s):  
Chloride Ion ◽  
Chloride Ion Influx ◽  
Ion Influx

Characteristics of chloride ion influx in Amphiuma small intestine

1989 ◽  
Vol 256 (1) ◽  
pp. G166-G177 ◽  
Author(s):  
J. F. White
Keyword(s):  
Small Intestine ◽  
Chloride Ion ◽  
Disulfonic Acid ◽  
Ionophore A23187 ◽  
Bathing Medium ◽  
Luminal Membrane ◽  
Chloride Ion Influx ◽  
Ion Influx ◽  
Ethanesulfonic Acid ◽  
Dependent Pathway

Net Cl- absorption by Amphiuma small intestine is electrogenic but associated with the secretion of HCO3-. To define the mechanisms of Cl- entry into the enterocytes the initial rate of uptake of 36Cl into isolated segments of small intestine was measured. Luminal extracellular space was measured using [3H]inulin. Cl- influx was saturable with a Km of 5.3 mM. When the mucosal medium Cl- concentration was 20 mM influx was linear for 5 min. Cl- influx in 5 min (JiCl) was not reduced by 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid added to the serosal medium, although the Cl- current was abolished. Hence the luminal membrane was the barrier to Cl- uptake. Monovalent anions blocked Cl- influx in the order I- = SCN- = NO3- greater than Br- greater than F-. Anoxia and dinitrophenol reduced JiCl 33 and 71%, respectively. Substitution of medium Na+ with choline or N-methyl glucamine reduced JiCl 60-70%. Removal of medium K+ reduced influx 51%. After medium Na+ and K+ were both replaced influx was stimulated upon reexposure to (Na+ + K+); Na+ alone did not stimulate. JiCl was reduced 34% by furosemide. Neither amiloride nor SITS in the mucosal medium altered influx. JiCl was reduced by replacement of the HCO3- -CO2 buffer with either phosphate or N-2-hydroxyethyl-piperazine-N'-2-ethanesulfonic acid and by exposure to acetazolamide. Theophylline reduced influx 60%, whereas the Ca ionophore A23187 reduced net Cl- absorption and lowered JiCl by 17%. Norepinephrine (10(-5) M) in the serosal bathing medium stimulated Cl- influx 51%. These results indicate that Cl- influx into the intestinal mucosa occurs by a Na+- and, possibly, K+-dependent pathway. Cl- entry is under adrenergic influence.

Effect of penicillin on GABA-gated chloride ion influx

1994 ◽  
Vol 19 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Akemi Tsuda ◽  
Masatoshi Ito ◽  
Kazuko Kishi ◽  
Hideyuki Shiraishi ◽  
Hideo Tsuda ◽  
...  
Keyword(s):  
Chloride Ion ◽  
Chloride Ion Influx ◽  
Ion Influx
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