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Brian Collier - One of the best experts on this subject based on the ideXlab platform.
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RegulatIon of Rat Brain Synaptosomal [3H]Hemicholinium‐3 Binding and [3H]Choline Transport Sites Following Exposure to Choline Mustard Aziridinium Ion
Journal of Neurochemistry, 2002Co-Authors: S. S. G. Ferguson, R. Jane Rylett, Brian CollierAbstract:: Choline uptake by cholinergic nerve terminals is increased by depolarizatIon; the literature suggests that this results from either the appearance of occult transporters or the increased activity of existing ones. The present experiments attempt to clarify the mechanism by which choline transport is regulated by testing if the preexposure of synaptosomes to choline mustard Aziridinium Ion prevents the stimulatIon-induced appearance of hemicholinium-3 binding sites and/or choline transport activity. Choline mustard inhibited irreversibly most of the "ground-state" (basal) high-affinity choline transport but only 50% of "ground-state" hemicholinium-3 binding sites. Exposure of both striatal and hippocampal synaptosomes to the mustard, before stimulatIon, inhibited K(+)-stimulated increases in choline transport and of [3H]-hemicholinium-3 binding. We conclude that the mechanism by which choline transport is regulated involves the increased activity of a pool of transport sites that are occluded to hemicholinium-3 but are available to choline mustard Aziridinium Ion, and presumably to choline, before stimulatIon. However, the concentratIon of mustard needed to inhibit the stimulatIon-induced increase of [3H]-hemicholinium-3 binding and choline transport was lower for striatal synaptosomes than for hippocampal synaptosomes. In the absence of extracellular Ca2+ or presence of high Mg2+ levels, the choline mustard did not prevent the appearance of extra striatal hemicholinium-3 binding sites. Also, high Mg2+ levels removed the ability of the mustard to inhibit K(+)-stimulated increases of either [3H]-hemicholinium-3 binding or choline transport by hippocampal synaptosomes. In contrast, the preexposure of hippocampal synaptosomes to the mustard in the presence of a calcium Ionophore (A23187) reduced the concentratIon of inhibitor needed to prevent the activatIon of [3H]hemicholinium-3 binding and choline uptake. Thus, we conclude that the ability of the choline mustard to alkylate the pool of choline transporters that are activated by stimulatIon appears dependent on the entry of extra-cellular Ca2+.
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regulatIon of rat brain synaptosomal 3h hemicholinium 3 binding and 3h choline transport sites following exposure to choline mustard Aziridinium Ion
Journal of Neurochemistry, 2002Co-Authors: S. S. G. Ferguson, R.j. Rylett, Brian CollierAbstract:Choline uptake by cholinergic nerve terminals is increased by depolarizatIon; the literature suggests that this results from either the appearance of occult transporters or the increased activity of existing ones. The present experiments attempt to clarify the mechanism by which choline transport is regulated by testing if the preexposure of synaptosomes to choline mustard Aziridinium Ion prevents the stimulatIon-induced appearance of hemicholinium-3 binding sites and/or choline transport activity. Choline mustard inhibited irreversibly most of the "ground-state" (basal) high-affinity choline transport but only 50% of "ground-state" hemicholinium-3 binding sites. Exposure of both striatal and hippocampal synaptosomes to the mustard, before stimulatIon, inhibited K(+)-stimulated increases in choline transport and of [3H]-hemicholinium-3 binding. We conclude that the mechanism by which choline transport is regulated involves the increased activity of a pool of transport sites that are occluded to hemicholinium-3 but are available to choline mustard Aziridinium Ion, and presumably to choline, before stimulatIon. However, the concentratIon of mustard needed to inhibit the stimulatIon-induced increase of [3H]-hemicholinium-3 binding and choline transport was lower for striatal synaptosomes than for hippocampal synaptosomes. In the absence of extracellular Ca2+ or presence of high Mg2+ levels, the choline mustard did not prevent the appearance of extra striatal hemicholinium-3 binding sites. Also, high Mg2+ levels removed the ability of the mustard to inhibit K(+)-stimulated increases of either [3H]-hemicholinium-3 binding or choline transport by hippocampal synaptosomes. In contrast, the preexposure of hippocampal synaptosomes to the mustard in the presence of a calcium Ionophore (A23187) reduced the concentratIon of inhibitor needed to prevent the activatIon of [3H]hemicholinium-3 binding and choline uptake. Thus, we conclude that the ability of the choline mustard to alkylate the pool of choline transporters that are activated by stimulatIon appears dependent on the entry of extra-cellular Ca2+.
Tadanobu Itoh - One of the best experts on this subject based on the ideXlab platform.
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Reversal by 3,3′,5-triido-l-thyronine of the working memory deficit, and the decrease in acetylcholine, glutamate and γ-aminobutyric acid induced by ethylcholine Aziridinium Ion in mice
Naunyn-Schmiedeberg's Archives of Pharmacology, 1992Co-Authors: Eiichi Abe, Yoshikatsu Masuda, Shigeo Murai, Hiroko Saito, Tadanobu ItohAbstract:The effect of 3,3′,5-triiodo- l -thyronine (T_3) on working memory in ethylcholine Aziridinium Ion (AF64A)-treated mice was studied in a delayed nonmatching to sample task using a T-maze. After behavioural testing was completed, mice were killed by microwave irradiatIon and regIonal brain levels of acetylcholine, aspartate, glutamate, glutamine, glycine, taurine, and γ-aminobutyric acid (GABA) were measured by high-performance liquid chromatography with electrochemical detectIon. Treatment with AF64A (7 nmol, i. c. v.) produced a deficit in working memory performance in the non-matching to sample task at 30 s delay, and decreased acetylcholine, glutamate, and GABA levels in the hippocampus, but not in the septum and cerebral cortex. AdministratIon of T_3 (0.3 mg/kg, p.o., once daily for 6 days) to AF64A-treated animals improved the deficit in working memory performance and reversed the decrease in acetylcholine, glutamate, and GABA levels in the hippocampus. These results indicate that the deficit in performance induced by AF64A can be improved by T_3 administratIon.
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A simple T-maze method for estimating working memory in mice. Effect of ethylcholine mustard Aziridinium Ion (AF64A).
Journal of pharmacological and toxicological methods, 1992Co-Authors: Yoshikatsu Masuda, Shigeo Murai, Hiroko Saito, Eiichi Abe, Tadanobu ItohAbstract:Abstract Mice were housed in a cage containing a T maze. A watering place was located at the entrance of the maze. The right and left arms of the maze each had two exits, one of which led to the home cage where food was placed, while the other led to the watering place via a bypass. The exit leading to the home cage in either the right or left arm was alternately closed every 90 min. One-way swinging doors were inserted at the entrance arm and between each bypass and the watering place. The mice were given a cholinergic neurotoxin—ethylcholine mustard Aziridinium Ion (AF64A)—(8 nmol) or saline as a control into the left ventricle 2 weeks before they were housed in the apparatus. Those mice housed in this apparatus mastered the alternatIon task at a 5-sec delay on day 3 in the sham group and on day 4 in the AF64A group. When a longer delay (5–90 sec) was introduced for the mice that mastered the alternatIon task at 5-sec delay, the AF64A group made significantly more errors than did the sham group at 60- and 90-sec delays. These results show that the apparatus is useful in estimating working memory in mice with little effort.
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Reversal by 3,3',5-triido-L-thyronine of the working memory deficit, and the decrease in acetylcholine, glutamate and gamma-aminobutyric acid induced by ethylcholine Aziridinium Ion in mice.
Naunyn-Schmiedeberg's archives of pharmacology, 1992Co-Authors: Eiichi Abe, Yoshikatsu Masuda, Shigeo Murai, Hiroko Saito, Tadanobu ItohAbstract:The effect of 3,3',5-triiodo-L-thyronine (T3) on working memory in ethylcholine Aziridinium Ion (AF64A)-treated mice was studied in a delayed non-matching to sample task using a T-maze. After behavioural testing was completed, mice were killed by microwave irradiatIon and regIonal brain levels of acetylcholine, aspartate, glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid (GABA) were measured by high-performance liquid chromatography with electrochemical detectIon. Treatment with AF64A (7 nmol, i.c.v.) produced a deficit in working memory performance in the non-matching to sample task at 30 s delay, and decreased acetylcholine, glutamate, and GABA levels in the hippocampus, but not in the septum and cerebral cortex. AdministratIon of T3 (0.3 mg/kg, p.o., once daily for 6 days) to AF64A-treated animals improved the deficit in working memory performance and reversed the decrease in acetylcholine, glutamate, and GABA levels in the hippocampus. These results indicate that the deficit in performance induced by AF64A can be improved by T3 administratIon.
S. S. G. Ferguson - One of the best experts on this subject based on the ideXlab platform.
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RegulatIon of Rat Brain Synaptosomal [3H]Hemicholinium‐3 Binding and [3H]Choline Transport Sites Following Exposure to Choline Mustard Aziridinium Ion
Journal of Neurochemistry, 2002Co-Authors: S. S. G. Ferguson, R. Jane Rylett, Brian CollierAbstract:: Choline uptake by cholinergic nerve terminals is increased by depolarizatIon; the literature suggests that this results from either the appearance of occult transporters or the increased activity of existing ones. The present experiments attempt to clarify the mechanism by which choline transport is regulated by testing if the preexposure of synaptosomes to choline mustard Aziridinium Ion prevents the stimulatIon-induced appearance of hemicholinium-3 binding sites and/or choline transport activity. Choline mustard inhibited irreversibly most of the "ground-state" (basal) high-affinity choline transport but only 50% of "ground-state" hemicholinium-3 binding sites. Exposure of both striatal and hippocampal synaptosomes to the mustard, before stimulatIon, inhibited K(+)-stimulated increases in choline transport and of [3H]-hemicholinium-3 binding. We conclude that the mechanism by which choline transport is regulated involves the increased activity of a pool of transport sites that are occluded to hemicholinium-3 but are available to choline mustard Aziridinium Ion, and presumably to choline, before stimulatIon. However, the concentratIon of mustard needed to inhibit the stimulatIon-induced increase of [3H]-hemicholinium-3 binding and choline transport was lower for striatal synaptosomes than for hippocampal synaptosomes. In the absence of extracellular Ca2+ or presence of high Mg2+ levels, the choline mustard did not prevent the appearance of extra striatal hemicholinium-3 binding sites. Also, high Mg2+ levels removed the ability of the mustard to inhibit K(+)-stimulated increases of either [3H]-hemicholinium-3 binding or choline transport by hippocampal synaptosomes. In contrast, the preexposure of hippocampal synaptosomes to the mustard in the presence of a calcium Ionophore (A23187) reduced the concentratIon of inhibitor needed to prevent the activatIon of [3H]hemicholinium-3 binding and choline uptake. Thus, we conclude that the ability of the choline mustard to alkylate the pool of choline transporters that are activated by stimulatIon appears dependent on the entry of extra-cellular Ca2+.
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regulatIon of rat brain synaptosomal 3h hemicholinium 3 binding and 3h choline transport sites following exposure to choline mustard Aziridinium Ion
Journal of Neurochemistry, 2002Co-Authors: S. S. G. Ferguson, R.j. Rylett, Brian CollierAbstract:Choline uptake by cholinergic nerve terminals is increased by depolarizatIon; the literature suggests that this results from either the appearance of occult transporters or the increased activity of existing ones. The present experiments attempt to clarify the mechanism by which choline transport is regulated by testing if the preexposure of synaptosomes to choline mustard Aziridinium Ion prevents the stimulatIon-induced appearance of hemicholinium-3 binding sites and/or choline transport activity. Choline mustard inhibited irreversibly most of the "ground-state" (basal) high-affinity choline transport but only 50% of "ground-state" hemicholinium-3 binding sites. Exposure of both striatal and hippocampal synaptosomes to the mustard, before stimulatIon, inhibited K(+)-stimulated increases in choline transport and of [3H]-hemicholinium-3 binding. We conclude that the mechanism by which choline transport is regulated involves the increased activity of a pool of transport sites that are occluded to hemicholinium-3 but are available to choline mustard Aziridinium Ion, and presumably to choline, before stimulatIon. However, the concentratIon of mustard needed to inhibit the stimulatIon-induced increase of [3H]-hemicholinium-3 binding and choline transport was lower for striatal synaptosomes than for hippocampal synaptosomes. In the absence of extracellular Ca2+ or presence of high Mg2+ levels, the choline mustard did not prevent the appearance of extra striatal hemicholinium-3 binding sites. Also, high Mg2+ levels removed the ability of the mustard to inhibit K(+)-stimulated increases of either [3H]-hemicholinium-3 binding or choline transport by hippocampal synaptosomes. In contrast, the preexposure of hippocampal synaptosomes to the mustard in the presence of a calcium Ionophore (A23187) reduced the concentratIon of inhibitor needed to prevent the activatIon of [3H]hemicholinium-3 binding and choline uptake. Thus, we conclude that the ability of the choline mustard to alkylate the pool of choline transporters that are activated by stimulatIon appears dependent on the entry of extra-cellular Ca2+.
Christopher M. Rayner - One of the best experts on this subject based on the ideXlab platform.
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An iterative approach to novel polyamines via nucleophilic ring-opening of Aziridinium Ions with β-amino alcohols
Chemical communications (Cambridge England), 2004Co-Authors: Christopher Mckay, Robert J. Wilson, Christopher M. RaynerAbstract:An iterative procedure for the synthesis of a novel class of synthetic polyamines has been developed, utilising the regioselective ring-opening of Aziridinium Ion intermediates; facile N-allyl deprotectIon of intermediate polyamines allows the rapid constructIon of high molecular weight, stereochemically defined compounds in a convergent manner.
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Studies on the Lewis acid mediated cleavage of α-aminoacetals: synthesis of novel 1,2-aminoethers, and evidence for α-alkoxy Aziridinium Ion intermediates
Organic & biomolecular chemistry, 2003Co-Authors: Mark A. Graham, Alan H. Wadsworth, Abdul Zahid, Christopher M. RaynerAbstract:The nucleophilic cleavage of α-amino acetals induced by TMSOTf can be used to prepare a wide range of substituted 1,2-aminoethers. In particular, organometallic reagents, N-heterocycles, and enamines all react efficiently to give products in good yield. In appropriate cases, good levels of stereocontrol are possible, but this is very dependent on the nature of the nucleophile and the substrate, with diethylzinc proving particularly effective across a range of substrates. The degree of stereocontrol can be used to infer the nature of the reactive intermediates involved in the reactIon. With diethylzinc, it is most likely that the reactIon proceeds by coordinatIon of the nucleophile to the amino group followed by transfer of an ethyl group to an α-oxocarbenium Ion. With non-coordinating nucleophiles, the stereochemical outcome can be ratIonalised in terms of additIon to the possible α-alkoxy Aziridinium Ion intermediates.
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Tandem catIonic cyclisatIon–Aziridinium Ion formatIon–nucleophilicring opening: new methodology for the stereocontrolled synthesis of substitutedpyrrolidines
Chemical Communications, 2001Co-Authors: Mark A. Graham, Alan H. Wadsworth, Mark Thornton-pett, Christopher M. RaynerAbstract:A novel tandem catIonic cyclisatIon–Aziridinium Ion formatIon–nucleophilic ring opening procedure has been developed which provides powerful new methodology for the stereocontrolled synthesis of a wide variety of substituted pyrrolidines from acyclic precursors. The intermediate bicyclic Aziridinium Ions can be isolated and their structure has been confirmed by X-ray crystallography.
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tandem catIonic cyclisatIon Aziridinium Ion formatIon nucleophilicring opening new methodology for the stereocontrolled synthesis of substitutedpyrrolidines
Chemical Communications, 2001Co-Authors: Mark A. Graham, Alan H. Wadsworth, Mark Thorntonpett, Christopher M. RaynerAbstract:A novel tandem catIonic cyclisatIon–Aziridinium Ion formatIon–nucleophilic ring opening procedure has been developed which provides powerful new methodology for the stereocontrolled synthesis of a wide variety of substituted pyrrolidines from acyclic precursors. The intermediate bicyclic Aziridinium Ions can be isolated and their structure has been confirmed by X-ray crystallography.
Eiichi Abe - One of the best experts on this subject based on the ideXlab platform.
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Reversal by 3,3′,5-triido-l-thyronine of the working memory deficit, and the decrease in acetylcholine, glutamate and γ-aminobutyric acid induced by ethylcholine Aziridinium Ion in mice
Naunyn-Schmiedeberg's Archives of Pharmacology, 1992Co-Authors: Eiichi Abe, Yoshikatsu Masuda, Shigeo Murai, Hiroko Saito, Tadanobu ItohAbstract:The effect of 3,3′,5-triiodo- l -thyronine (T_3) on working memory in ethylcholine Aziridinium Ion (AF64A)-treated mice was studied in a delayed nonmatching to sample task using a T-maze. After behavioural testing was completed, mice were killed by microwave irradiatIon and regIonal brain levels of acetylcholine, aspartate, glutamate, glutamine, glycine, taurine, and γ-aminobutyric acid (GABA) were measured by high-performance liquid chromatography with electrochemical detectIon. Treatment with AF64A (7 nmol, i. c. v.) produced a deficit in working memory performance in the non-matching to sample task at 30 s delay, and decreased acetylcholine, glutamate, and GABA levels in the hippocampus, but not in the septum and cerebral cortex. AdministratIon of T_3 (0.3 mg/kg, p.o., once daily for 6 days) to AF64A-treated animals improved the deficit in working memory performance and reversed the decrease in acetylcholine, glutamate, and GABA levels in the hippocampus. These results indicate that the deficit in performance induced by AF64A can be improved by T_3 administratIon.
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A simple T-maze method for estimating working memory in mice. Effect of ethylcholine mustard Aziridinium Ion (AF64A).
Journal of pharmacological and toxicological methods, 1992Co-Authors: Yoshikatsu Masuda, Shigeo Murai, Hiroko Saito, Eiichi Abe, Tadanobu ItohAbstract:Abstract Mice were housed in a cage containing a T maze. A watering place was located at the entrance of the maze. The right and left arms of the maze each had two exits, one of which led to the home cage where food was placed, while the other led to the watering place via a bypass. The exit leading to the home cage in either the right or left arm was alternately closed every 90 min. One-way swinging doors were inserted at the entrance arm and between each bypass and the watering place. The mice were given a cholinergic neurotoxin—ethylcholine mustard Aziridinium Ion (AF64A)—(8 nmol) or saline as a control into the left ventricle 2 weeks before they were housed in the apparatus. Those mice housed in this apparatus mastered the alternatIon task at a 5-sec delay on day 3 in the sham group and on day 4 in the AF64A group. When a longer delay (5–90 sec) was introduced for the mice that mastered the alternatIon task at 5-sec delay, the AF64A group made significantly more errors than did the sham group at 60- and 90-sec delays. These results show that the apparatus is useful in estimating working memory in mice with little effort.
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Reversal by 3,3',5-triido-L-thyronine of the working memory deficit, and the decrease in acetylcholine, glutamate and gamma-aminobutyric acid induced by ethylcholine Aziridinium Ion in mice.
Naunyn-Schmiedeberg's archives of pharmacology, 1992Co-Authors: Eiichi Abe, Yoshikatsu Masuda, Shigeo Murai, Hiroko Saito, Tadanobu ItohAbstract:The effect of 3,3',5-triiodo-L-thyronine (T3) on working memory in ethylcholine Aziridinium Ion (AF64A)-treated mice was studied in a delayed non-matching to sample task using a T-maze. After behavioural testing was completed, mice were killed by microwave irradiatIon and regIonal brain levels of acetylcholine, aspartate, glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid (GABA) were measured by high-performance liquid chromatography with electrochemical detectIon. Treatment with AF64A (7 nmol, i.c.v.) produced a deficit in working memory performance in the non-matching to sample task at 30 s delay, and decreased acetylcholine, glutamate, and GABA levels in the hippocampus, but not in the septum and cerebral cortex. AdministratIon of T3 (0.3 mg/kg, p.o., once daily for 6 days) to AF64A-treated animals improved the deficit in working memory performance and reversed the decrease in acetylcholine, glutamate, and GABA levels in the hippocampus. These results indicate that the deficit in performance induced by AF64A can be improved by T3 administratIon.
