The Experts below are selected from a list of 168 Experts worldwide ranked by ideXlab platform
Cynthia Czajkowski - One of the best experts on this subject based on the ideXlab platform.
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γ aminobutyric acid gaba and Pentobarbital induce different conformational rearrangements in the gabaa receptor α1 and β2 pre m1 regions
Journal of Biological Chemistry, 2008Co-Authors: Jose Mercado, Cynthia CzajkowskiAbstract:Abstract γ-Aminobutyric acid (GABA) binding to GABAA receptors (GABAARs) triggers conformational movements in the α1 and β2 pre-M1 regions that are associated with channel gating. At high concentrations, the barbiturate Pentobarbital opens GABAAR channels with similar conductances as GABA, suggesting that their open state structures are alike. Little, however, is known about the structural rearrangements induced by barbiturates. Here, we examined whether Pentobarbital activation triggers movements in the GABAAR pre-M1 regions. α1β2 GABAARs containing cysteine substitutions in the pre-M1 α1 (K219C, K221C) and β2 (K213C, K215C) subunits were expressed in Xenopus oocytes and analyzed using two-electrode voltage clamp. The cysteine substitutions had little to no effect on GABA and Pentobarbital EC50 values. Tethering chemically diverse thiol-reactive methanethiosulfonate reagents onto α1K219C and α1K221C affected GABA- and Pentobarbital-activated currents differently, suggesting that the pre-M1 structural elements important for GABA and Pentobarbital current activation are distinct. Moreover, Pentobarbital altered the rates of cysteine modification by methanethiosulfonate reagents differently than GABA. For α1K221Cβ2 receptors, Pentobarbital decreased the rate of cysteine modification whereas GABA had no effect. For α1β2K215C receptors, Pentobarbital had no effect whereas GABA increased the modification rate. The competitive GABA antagonist SR-95531 and a low, non-activating concentration of Pentobarbital did not alter their modification rates, suggesting that the GABA- and Pentobarbital-mediated changes in rates reflect gating movements. Overall, the data indicate that the pre-M1 region is involved in both GABA- and Pentobarbital-mediated gating transitions. Pentobarbital, however, triggers different movements in this region than GABA, suggesting their activation mechanisms differ.
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gamma aminobutyric acid gaba and Pentobarbital induce different conformational rearrangements in the gaba a receptor alpha1 and beta2 pre m1 regions
Journal of Biological Chemistry, 2008Co-Authors: Jose Mercado, Cynthia CzajkowskiAbstract:: Gamma-aminobutyric acid (GABA) binding to GABA(A) receptors (GABA(A)Rs) triggers conformational movements in the alpha(1) and beta(2) pre-M1 regions that are associated with channel gating. At high concentrations, the barbiturate Pentobarbital opens GABA(A)R channels with similar conductances as GABA, suggesting that their open state structures are alike. Little, however, is known about the structural rearrangements induced by barbiturates. Here, we examined whether Pentobarbital activation triggers movements in the GABA(A)R pre-M1 regions. Alpha(1)beta(2) GABA(A)Rs containing cysteine substitutions in the pre-M1 alpha(1) (K219C, K221C) and beta(2) (K213C, K215C) subunits were expressed in Xenopus oocytes and analyzed using two-electrode voltage clamp. The cysteine substitutions had little to no effect on GABA and Pentobarbital EC(50) values. Tethering chemically diverse thiol-reactive methanethiosulfonate reagents onto alpha(1)K219C and alpha(1)K221C affected GABA- and Pentobarbital-activated currents differently, suggesting that the pre-M1 structural elements important for GABA and Pentobarbital current activation are distinct. Moreover, Pentobarbital altered the rates of cysteine modification by methanethiosulfonate reagents differently than GABA. For alpha(1)K221Cbeta(2) receptors, Pentobarbital decreased the rate of cysteine modification whereas GABA had no effect. For alpha(1)beta(2)K215C receptors, Pentobarbital had no effect whereas GABA increased the modification rate. The competitive GABA antagonist SR-95531 and a low, non-activating concentration of Pentobarbital did not alter their modification rates, suggesting that the GABA- and Pentobarbital-mediated changes in rates reflect gating movements. Overall, the data indicate that the pre-M1 region is involved in both GABA- and Pentobarbital-mediated gating transitions. Pentobarbital, however, triggers different movements in this region than GABA, suggesting their activation mechanisms differ.
Kiwan Oh - One of the best experts on this subject based on the ideXlab platform.
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methanol extract of longanae arillus augments Pentobarbital induced sleep behaviors through the modification of gabaergic systems
Journal of Ethnopharmacology, 2009Co-Authors: Jintae Hong, Kiwan OhAbstract:Abstract This experiment was performed to investigate whether methanol extract of Longanae Arillus (MELA) has hypnotic effects and/or enhances Pentobarbital-induced sleep behaviors through the GABAergic systems. MELA prolonged sleep time and reduced sleep latency induced by Pentobarbital similar to muscimol, a GABAA receptors agonist. MELA also increased sleep rate and sleep time in the combined administration with Pentobarbital at the sub-hypnotic dosage and showed synergic effects with muscimol in potentiating sleep onset and enhancing sleep time induced by Pentobarbital. However, MELA itself did not induce sleep at higher dose which was used in this experiment. In addition, both of MELA and Pentobarbital increased chloride influx in primary cultured cerebellar granule cells. MELA increased GABAA receptors γ-subunit expression and had no effect on the expression of α- and β-subunits, and glutamic acid decarboxylase (GAD) in primary cultured cerebellar granule cells, showing different expression of subunits from Pentobarbital. In conclusion, MELA itself does not induce sleep, but it augments Pentobarbital-induced sleep behaviors through the modification of GABAergic systems.
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cyclopeptide alkaloid fraction from zizyphi spinosi semen enhances Pentobarbital induced sleeping behaviors
Journal of Ethnopharmacology, 2008Co-Authors: Jintae Hong, Kiwan OhAbstract:Abstract This study aimed to investigate effects of cyclopeptide alkaloid fraction of ZSS (CAFZ) on Pentobarbital-induced sleeping behaviors and to determine whether these effects were mediated by γ-aminobutyric acid (GABA) receptors Cl − channel activation, using a Western blot technique and Cl − sensitive fluorescence probe. GABA receptors subunits expression and Cl − influx were investigated in cultured cerebellar granule cells. CAFZ shortened sleeping onset and prolonged sleeping time induced by Pentobarbital (42 mg/kg). It also significantly increased the falling asleep rate and duration of sleeping time at a sub-hypnotic dosage of Pentobarbital (28 mg/kg). In addition, CAFZ in combination with GABA A receptors agonist, muscimol, synergistically prolonged Pentobarbital-induced sleeping time. Both of CAFZ and Pentobarbital treatment decreased GABA A receptors α-subunit expression, but did not change β- and γ-subunit expression. However, we found CAFZ and Pentobarbital increased Cl − influx, CAFZ showed similar effects with muscimol in potentiating Cl − influx inducing effects of low-dose Pentobarbital. In conclusion, it is suggested that the enhancement of Cl − influx by CAFZ may play an important role in the potentiation of Pentobarbital-induced sleeping behaviors.
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sanjoinine a isolated from zizyphi spinosi semen augments Pentobarbital induced sleeping behaviors through the modification of gaba ergic systems
Biological & Pharmaceutical Bulletin, 2007Co-Authors: Jintae Hong, Kiwan OhAbstract:: Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of insomnia in oriental countries. This experiment was performed to investigate whether sanjoinine A, one of major alkaloid compounds of ZSS, has hypnotic effects and/or enhances Pentobarbital-induced sleeping behaviors through the gamma-aminobutyric acid (GABA)-ergic systems. Sanjoinine A itself did not induce sleeping at the higher dose used in this experiment. However, sanjoinine A prolonged sleeping time and reduced the sleeping latency induced by Pentobarbital in a dose-dependent manner similar to muscimol, a GABA(A) receptor agonist. Sanjoinine A also increased sleeping rate and sleeping time when administered combined with Pentobarbital at a sub-hypnotic dosage and showed synergistic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by Pentobarbital. In addition, both sanjoinine A and Pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A also showed similar effects with muscimol in potentiating chloride influx inducing effects of low dose Pentobarbital. Sanjoinine A decreased GABA(A) receptor alpha-subunit expression and increased gamma-subunit expression, and had no effects on the abundance of beta-subunits in primary cultured cerebellar granule cells, showing different subunit expression from Pentobarbital. In addition, we found that sanjoinine A also enhanced expression of glutamic acid decarboxylase (GAD), but Pentobarbital did not. In conclusion, sanjoinine A itself does not induce sleeping, but it augments Pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems.
Jose Mercado - One of the best experts on this subject based on the ideXlab platform.
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γ aminobutyric acid gaba and Pentobarbital induce different conformational rearrangements in the gabaa receptor α1 and β2 pre m1 regions
Journal of Biological Chemistry, 2008Co-Authors: Jose Mercado, Cynthia CzajkowskiAbstract:Abstract γ-Aminobutyric acid (GABA) binding to GABAA receptors (GABAARs) triggers conformational movements in the α1 and β2 pre-M1 regions that are associated with channel gating. At high concentrations, the barbiturate Pentobarbital opens GABAAR channels with similar conductances as GABA, suggesting that their open state structures are alike. Little, however, is known about the structural rearrangements induced by barbiturates. Here, we examined whether Pentobarbital activation triggers movements in the GABAAR pre-M1 regions. α1β2 GABAARs containing cysteine substitutions in the pre-M1 α1 (K219C, K221C) and β2 (K213C, K215C) subunits were expressed in Xenopus oocytes and analyzed using two-electrode voltage clamp. The cysteine substitutions had little to no effect on GABA and Pentobarbital EC50 values. Tethering chemically diverse thiol-reactive methanethiosulfonate reagents onto α1K219C and α1K221C affected GABA- and Pentobarbital-activated currents differently, suggesting that the pre-M1 structural elements important for GABA and Pentobarbital current activation are distinct. Moreover, Pentobarbital altered the rates of cysteine modification by methanethiosulfonate reagents differently than GABA. For α1K221Cβ2 receptors, Pentobarbital decreased the rate of cysteine modification whereas GABA had no effect. For α1β2K215C receptors, Pentobarbital had no effect whereas GABA increased the modification rate. The competitive GABA antagonist SR-95531 and a low, non-activating concentration of Pentobarbital did not alter their modification rates, suggesting that the GABA- and Pentobarbital-mediated changes in rates reflect gating movements. Overall, the data indicate that the pre-M1 region is involved in both GABA- and Pentobarbital-mediated gating transitions. Pentobarbital, however, triggers different movements in this region than GABA, suggesting their activation mechanisms differ.
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gamma aminobutyric acid gaba and Pentobarbital induce different conformational rearrangements in the gaba a receptor alpha1 and beta2 pre m1 regions
Journal of Biological Chemistry, 2008Co-Authors: Jose Mercado, Cynthia CzajkowskiAbstract:: Gamma-aminobutyric acid (GABA) binding to GABA(A) receptors (GABA(A)Rs) triggers conformational movements in the alpha(1) and beta(2) pre-M1 regions that are associated with channel gating. At high concentrations, the barbiturate Pentobarbital opens GABA(A)R channels with similar conductances as GABA, suggesting that their open state structures are alike. Little, however, is known about the structural rearrangements induced by barbiturates. Here, we examined whether Pentobarbital activation triggers movements in the GABA(A)R pre-M1 regions. Alpha(1)beta(2) GABA(A)Rs containing cysteine substitutions in the pre-M1 alpha(1) (K219C, K221C) and beta(2) (K213C, K215C) subunits were expressed in Xenopus oocytes and analyzed using two-electrode voltage clamp. The cysteine substitutions had little to no effect on GABA and Pentobarbital EC(50) values. Tethering chemically diverse thiol-reactive methanethiosulfonate reagents onto alpha(1)K219C and alpha(1)K221C affected GABA- and Pentobarbital-activated currents differently, suggesting that the pre-M1 structural elements important for GABA and Pentobarbital current activation are distinct. Moreover, Pentobarbital altered the rates of cysteine modification by methanethiosulfonate reagents differently than GABA. For alpha(1)K221Cbeta(2) receptors, Pentobarbital decreased the rate of cysteine modification whereas GABA had no effect. For alpha(1)beta(2)K215C receptors, Pentobarbital had no effect whereas GABA increased the modification rate. The competitive GABA antagonist SR-95531 and a low, non-activating concentration of Pentobarbital did not alter their modification rates, suggesting that the GABA- and Pentobarbital-mediated changes in rates reflect gating movements. Overall, the data indicate that the pre-M1 region is involved in both GABA- and Pentobarbital-mediated gating transitions. Pentobarbital, however, triggers different movements in this region than GABA, suggesting their activation mechanisms differ.
Seikwan Oh - One of the best experts on this subject based on the ideXlab platform.
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Changes of [^3H]Muscimol Binding and GABA_A Receptor β2-Subunit mRNA Level by Tolerance to and Withdrawal from Pentobarbital in Rats
Neurochemical Research, 1999Co-Authors: Seikwan Oh, Ing K. HoAbstract:Effects of continuous Pentobarbital administration on binding characteristics of [^3H]muscimol were examined by autoradiography, and levels of GABA_A receptor β2-subunit mRNA were investigated by in situ hybridization histochemistry in the rat brain. In order to eliminate the induction of hepatic metabolism by systemic administration of Pentobarbital, an i.c.v. infusion model of tolerance to and withdrawal from Pentobarbital was used. An experimental model of barbiturate tolerance and withdrawal was developed using i.c.v. infusion of Pentobarbital (300 μg/10 μl/hr for 7 days) by osmotic minipumps and abrupt withdrawal from Pentobarbital. The levels of [^3H]muscimol binding were elevated in cingulate of frontal cortex (46%) and granule layer of cerebellum (32%) of rats 24-hr after withdrawal from Pentobarbital, while it was only elevated in cingulate (58%) of tolerant rats. The GABA_A receptor β2-subunit mRNA was increased in the withdrawal rats only: in the cortex (9–14%), hippocampus (15–21%), inferior colliculus (21%), and granule layer of cerebellum (24%). These results show the involvement of GABA_A receptor and its β2-subunit up-regulations in Pentobarbital withdrawal rats, and suggest that the levels of [^3H]muscimol binding and GABA_A receptor β2-subunit mRNA are altered in a region-specific manner during Pentobarbital withdrawal.
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Changes in NMDAR2 Subunit mRNA Levels During Pentobarbital Tolerance/Withdrawal in the Rat Brain: An In Situ Hybridization Study
Neurochemical Research, 1998Co-Authors: Choon-gon Jang, Seikwan Oh, Ing Kang HoAbstract:Little is known about the functional modulation of NMDA receptor subunits at the molecular level. Therefore, a series of experiments were conducted to elucidate more fully the role of NMDA receptor subtypes in Pentobarbital tolerance and withdrawal. We investigated the influence of centrally administered Pentobarbital on the regulation of mRNA levels of the family of NMDA receptor 2 (NR2) subtypes (NR2A, NR2B, and NR2C) by in situ hybridization histochemistry in rat brain. Animals were rendered tolerant by continuous intracerebroventricular (i.c.v.) infusion with Pentobarbital (300 μg/10 μl/hr for 6 days) through pre-implanted cannulae connected to osmotic mini-pumps, and dependent, by abrupt withdrawal from Pentobarbital. The NR2A subunit mRNA was increased in cortical areas in Pentobarbital tolerant and withdrawal rats. In contrast, the NR2B mRNA was decreased in parietal cortex and hippocampus in both tolerance and withdrawal rats. The level of NR2C mRNA was increased in withdrawal rats, while there was no change in tolerant rats. These results indicate that continuous i.c.v. infusion with Pentobarbital alters NR2 subunit mRNA expression in the rat brain, suggesting that NR2 subunits may play an important role in the development of tolerance to and withdrawal from Pentobarbital.
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Role of NMDA receptors in Pentobarbital tolerance/dependence.
Neurochemical Research, 1997Co-Authors: Seikwan Oh, Katsuji Hoshi, Ing Kang HoAbstract:Effects of continuous Pentobarbital administration on binding characteristics of [3H]MK-801 in the rat brain were examined by autoradiography. Animals were rendered tolerant to Pentobarbital using i.c.v. infusion of Pentobarbital (300μg/10μl/hr for 7 days) by osmotic minipumps and dependent by abrupt withdrawal from Pentobarbital. The levels of [3H]MK-801 binding were elevated in rats 24-hr after withdrawal from Pentobarbital while there were no changes except in septum and anterior ventral nuclei in tolerant rats. For assessing the role of NMDA receptor in barbiturate action, an NMDA receptor antagonist (MK-801, 2.7 femto g/10μl/hr) was co-infused with Pentobarbital. The Pentobarbital-infused group had a shorter duration of Pentobarbital-induced loss of righting reflex (sleeping time) than that of the control group, and MK-801 alone did not affect the righting reflex. However, co-infusion of MK-801 blocked hyperthermia, and prolonged the onset of convulsions induced by t-butylbicyclophosphorothionate (TBPS) in Pentobarbital withdrawal rats. In addition, elevated [35S]TBPS binding was significantly attenuated by co-infusion with MK-801. These results suggest the involvement of NMDA receptor up-regulation in Pentobarbital withdrawal and that the development of dependence can be attenuated by the treatment of subtoxic dose of MK-801.
Jintae Hong - One of the best experts on this subject based on the ideXlab platform.
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methanol extract of longanae arillus augments Pentobarbital induced sleep behaviors through the modification of gabaergic systems
Journal of Ethnopharmacology, 2009Co-Authors: Jintae Hong, Kiwan OhAbstract:Abstract This experiment was performed to investigate whether methanol extract of Longanae Arillus (MELA) has hypnotic effects and/or enhances Pentobarbital-induced sleep behaviors through the GABAergic systems. MELA prolonged sleep time and reduced sleep latency induced by Pentobarbital similar to muscimol, a GABAA receptors agonist. MELA also increased sleep rate and sleep time in the combined administration with Pentobarbital at the sub-hypnotic dosage and showed synergic effects with muscimol in potentiating sleep onset and enhancing sleep time induced by Pentobarbital. However, MELA itself did not induce sleep at higher dose which was used in this experiment. In addition, both of MELA and Pentobarbital increased chloride influx in primary cultured cerebellar granule cells. MELA increased GABAA receptors γ-subunit expression and had no effect on the expression of α- and β-subunits, and glutamic acid decarboxylase (GAD) in primary cultured cerebellar granule cells, showing different expression of subunits from Pentobarbital. In conclusion, MELA itself does not induce sleep, but it augments Pentobarbital-induced sleep behaviors through the modification of GABAergic systems.
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cyclopeptide alkaloid fraction from zizyphi spinosi semen enhances Pentobarbital induced sleeping behaviors
Journal of Ethnopharmacology, 2008Co-Authors: Jintae Hong, Kiwan OhAbstract:Abstract This study aimed to investigate effects of cyclopeptide alkaloid fraction of ZSS (CAFZ) on Pentobarbital-induced sleeping behaviors and to determine whether these effects were mediated by γ-aminobutyric acid (GABA) receptors Cl − channel activation, using a Western blot technique and Cl − sensitive fluorescence probe. GABA receptors subunits expression and Cl − influx were investigated in cultured cerebellar granule cells. CAFZ shortened sleeping onset and prolonged sleeping time induced by Pentobarbital (42 mg/kg). It also significantly increased the falling asleep rate and duration of sleeping time at a sub-hypnotic dosage of Pentobarbital (28 mg/kg). In addition, CAFZ in combination with GABA A receptors agonist, muscimol, synergistically prolonged Pentobarbital-induced sleeping time. Both of CAFZ and Pentobarbital treatment decreased GABA A receptors α-subunit expression, but did not change β- and γ-subunit expression. However, we found CAFZ and Pentobarbital increased Cl − influx, CAFZ showed similar effects with muscimol in potentiating Cl − influx inducing effects of low-dose Pentobarbital. In conclusion, it is suggested that the enhancement of Cl − influx by CAFZ may play an important role in the potentiation of Pentobarbital-induced sleeping behaviors.
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sanjoinine a isolated from zizyphi spinosi semen augments Pentobarbital induced sleeping behaviors through the modification of gaba ergic systems
Biological & Pharmaceutical Bulletin, 2007Co-Authors: Jintae Hong, Kiwan OhAbstract:: Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of insomnia in oriental countries. This experiment was performed to investigate whether sanjoinine A, one of major alkaloid compounds of ZSS, has hypnotic effects and/or enhances Pentobarbital-induced sleeping behaviors through the gamma-aminobutyric acid (GABA)-ergic systems. Sanjoinine A itself did not induce sleeping at the higher dose used in this experiment. However, sanjoinine A prolonged sleeping time and reduced the sleeping latency induced by Pentobarbital in a dose-dependent manner similar to muscimol, a GABA(A) receptor agonist. Sanjoinine A also increased sleeping rate and sleeping time when administered combined with Pentobarbital at a sub-hypnotic dosage and showed synergistic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by Pentobarbital. In addition, both sanjoinine A and Pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A also showed similar effects with muscimol in potentiating chloride influx inducing effects of low dose Pentobarbital. Sanjoinine A decreased GABA(A) receptor alpha-subunit expression and increased gamma-subunit expression, and had no effects on the abundance of beta-subunits in primary cultured cerebellar granule cells, showing different subunit expression from Pentobarbital. In addition, we found that sanjoinine A also enhanced expression of glutamic acid decarboxylase (GAD), but Pentobarbital did not. In conclusion, sanjoinine A itself does not induce sleeping, but it augments Pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems.
