Evaluation of radiolabeled acetylcholine synthesis and release in rat striatum
Cholinergic transmission underlies higher brain functions such as cognition and movement. To elucidate the process whereby acetylcholine (ACh) release is maintained and regulated in the central nervous system, uptake of [3H]choline and subsequent synthesis and release of [3H]ACh were investigated in...
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| Veröffentlicht in: | Journal of neurochemistry 2022-02, Vol.160 (3), p.342-355 |
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| creator | Muramatsu, Ikunobu Uwada, Junsuke Chihara, Kazuyasu Sada, Kiyonao Wang, Mao‐Hsien Yazawa, Takashi Taniguchi, Takanobu Ishibashi, Takaharu Masuoka, Takayoshi |
| description | Cholinergic transmission underlies higher brain functions such as cognition and movement. To elucidate the process whereby acetylcholine (ACh) release is maintained and regulated in the central nervous system, uptake of [3H]choline and subsequent synthesis and release of [3H]ACh were investigated in rat striatal segments. Incubation with [3H]choline elicited efficient uptake via high‐affinity choline transporter‐1, resulting in accumulation of [3H]choline and [3H]ACh. However, following inhibition of ACh esterase (AChE), incubation with [3H]choline led predominantly to the accumulation of [3H]ACh. Electrical stimulation and KCl depolarization selectively released [3H]ACh but not [3H]choline. [3H]ACh release gradually declined upon repetitive stimulation, whereas the release was reproducible under inhibition of AChE. [3H]ACh release was abolished after treatment with vesamicol, an inhibitor of vesicular ACh transporter. These results suggest that releasable ACh is continually replenished from the cytosol to releasable pools of cholinergic vesicles to maintain cholinergic transmission. [3H]ACh release evoked by electrical stimulation was abolished by tetrodotoxin, but that induced by KCl was largely resistant. ACh release was Ca2+ dependent and exhibited slightly different sensitivities to N‐ and P‐type Ca2+ channel toxins (ω‐conotoxin GVIA and ω‐agatoxin IVA, respectively) between both stimuli. [3H]ACh release was negatively regulated by M2 muscarinic and D2 dopaminergic receptors. The present results suggest that inhibition of AChE within cholinergic neurons and of presynaptic negative regulation of ACh release contributes to maintenance and facilitation of cholinergic transmission, providing a potentially useful clue for the development of therapies for cholinergic dysfunction‐associated disorders, in addition to inhibition of synaptic cleft AChE.
Sustainability of acetylcholine (ACh) release and its regulation in rat striatum were examined. Choline is constitutively supplied into cholinergic terminals through CHT1 and utilized for ACh synthesis. Synthesized ACh is stored in releasable and reserve pools, and excess ACh is degraded by cytosolic AChE. ACh release from releasable pool is negatively regulated by presynaptic M2‐muscarinic (M2R) and D2‐dopaminergic (D2R) receptors. Inhibition of cytosolic AChE and subsequent enhancement of ACh replenishment to releasable pool may contribute to the maintenance and facilitation of cholinergic transmission, in add |
| doi_str_mv | 10.1111/jnc.15556 |
| format | Article |
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Sustainability of acetylcholine (ACh) release and its regulation in rat striatum were examined. Choline is constitutively supplied into cholinergic terminals through CHT1 and utilized for ACh synthesis. Synthesized ACh is stored in releasable and reserve pools, and excess ACh is degraded by cytosolic AChE. ACh release from releasable pool is negatively regulated by presynaptic M2‐muscarinic (M2R) and D2‐dopaminergic (D2R) receptors. Inhibition of cytosolic AChE and subsequent enhancement of ACh replenishment to releasable pool may contribute to the maintenance and facilitation of cholinergic transmission, in addition to inhibitions of presynaptic negative feedback and synaptic cleft AChE.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/jnc.15556</identifier><identifier>PMID: 34878648</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Accumulation ; Acetylcholine ; Acetylcholine - biosynthesis ; acetylcholine esterase ; Acetylcholine receptors (muscarinic) ; Acetylcholinesterase ; Acetylcholinesterase - metabolism ; Animals ; Calcium Channel Blockers - pharmacology ; Calcium ions ; Central nervous system ; Choline ; Choline - metabolism ; cholinergic release ; Cholinergic transmission ; Cholinergics ; Cholinesterase Inhibitors - pharmacology ; Cognition ; Cytosol ; Depolarization ; Dopamine D2 receptors ; Electric Stimulation ; Electrical stimuli ; Esterase ; Male ; Neostriatum ; Neostriatum - metabolism ; Potassium chloride ; Potassium Chloride - pharmacology ; presynaptic modulation ; Radiopharmaceuticals ; Rats ; Rats, Wistar ; Receptor, Muscarinic M2 - drug effects ; Receptor, Muscarinic M2 - metabolism ; Receptors, Dopamine D1 - drug effects ; Receptors, Dopamine D1 - metabolism ; Stimulation ; striatum ; Synaptic cleft ; Synthesis ; Tetrodotoxin ; Toxins ; Vesamicol ; Vesicular Acetylcholine Transport Proteins - antagonists & inhibitors ; Vesicular Acetylcholine Transport Proteins - metabolism</subject><ispartof>Journal of neurochemistry, 2022-02, Vol.160 (3), p.342-355</ispartof><rights>2021 International Society for Neurochemistry</rights><rights>2021 International Society for Neurochemistry.</rights><rights>Copyright © 2022 International Society for Neurochemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4546-d37962873bce622bfaf1d629f2628520671f6bd7dfa5544ca11a35265686cd673</citedby><cites>FETCH-LOGICAL-c4546-d37962873bce622bfaf1d629f2628520671f6bd7dfa5544ca11a35265686cd673</cites><orcidid>0000-0002-6881-5391</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjnc.15556$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjnc.15556$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27903,27904,45553,45554,46387,46811</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34878648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muramatsu, Ikunobu</creatorcontrib><creatorcontrib>Uwada, Junsuke</creatorcontrib><creatorcontrib>Chihara, Kazuyasu</creatorcontrib><creatorcontrib>Sada, Kiyonao</creatorcontrib><creatorcontrib>Wang, Mao‐Hsien</creatorcontrib><creatorcontrib>Yazawa, Takashi</creatorcontrib><creatorcontrib>Taniguchi, Takanobu</creatorcontrib><creatorcontrib>Ishibashi, Takaharu</creatorcontrib><creatorcontrib>Masuoka, Takayoshi</creatorcontrib><title>Evaluation of radiolabeled acetylcholine synthesis and release in rat striatum</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>Cholinergic transmission underlies higher brain functions such as cognition and movement. To elucidate the process whereby acetylcholine (ACh) release is maintained and regulated in the central nervous system, uptake of [3H]choline and subsequent synthesis and release of [3H]ACh were investigated in rat striatal segments. Incubation with [3H]choline elicited efficient uptake via high‐affinity choline transporter‐1, resulting in accumulation of [3H]choline and [3H]ACh. However, following inhibition of ACh esterase (AChE), incubation with [3H]choline led predominantly to the accumulation of [3H]ACh. Electrical stimulation and KCl depolarization selectively released [3H]ACh but not [3H]choline. [3H]ACh release gradually declined upon repetitive stimulation, whereas the release was reproducible under inhibition of AChE. [3H]ACh release was abolished after treatment with vesamicol, an inhibitor of vesicular ACh transporter. These results suggest that releasable ACh is continually replenished from the cytosol to releasable pools of cholinergic vesicles to maintain cholinergic transmission. [3H]ACh release evoked by electrical stimulation was abolished by tetrodotoxin, but that induced by KCl was largely resistant. ACh release was Ca2+ dependent and exhibited slightly different sensitivities to N‐ and P‐type Ca2+ channel toxins (ω‐conotoxin GVIA and ω‐agatoxin IVA, respectively) between both stimuli. [3H]ACh release was negatively regulated by M2 muscarinic and D2 dopaminergic receptors. The present results suggest that inhibition of AChE within cholinergic neurons and of presynaptic negative regulation of ACh release contributes to maintenance and facilitation of cholinergic transmission, providing a potentially useful clue for the development of therapies for cholinergic dysfunction‐associated disorders, in addition to inhibition of synaptic cleft AChE.
Sustainability of acetylcholine (ACh) release and its regulation in rat striatum were examined. Choline is constitutively supplied into cholinergic terminals through CHT1 and utilized for ACh synthesis. Synthesized ACh is stored in releasable and reserve pools, and excess ACh is degraded by cytosolic AChE. ACh release from releasable pool is negatively regulated by presynaptic M2‐muscarinic (M2R) and D2‐dopaminergic (D2R) receptors. Inhibition of cytosolic AChE and subsequent enhancement of ACh replenishment to releasable pool may contribute to the maintenance and facilitation of cholinergic transmission, in addition to inhibitions of presynaptic negative feedback and synaptic cleft AChE.</description><subject>Accumulation</subject><subject>Acetylcholine</subject><subject>Acetylcholine - biosynthesis</subject><subject>acetylcholine esterase</subject><subject>Acetylcholine receptors (muscarinic)</subject><subject>Acetylcholinesterase</subject><subject>Acetylcholinesterase - metabolism</subject><subject>Animals</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium ions</subject><subject>Central nervous system</subject><subject>Choline</subject><subject>Choline - metabolism</subject><subject>cholinergic release</subject><subject>Cholinergic transmission</subject><subject>Cholinergics</subject><subject>Cholinesterase Inhibitors - pharmacology</subject><subject>Cognition</subject><subject>Cytosol</subject><subject>Depolarization</subject><subject>Dopamine D2 receptors</subject><subject>Electric Stimulation</subject><subject>Electrical stimuli</subject><subject>Esterase</subject><subject>Male</subject><subject>Neostriatum</subject><subject>Neostriatum - metabolism</subject><subject>Potassium chloride</subject><subject>Potassium Chloride - pharmacology</subject><subject>presynaptic modulation</subject><subject>Radiopharmaceuticals</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, Muscarinic M2 - drug effects</subject><subject>Receptor, Muscarinic M2 - metabolism</subject><subject>Receptors, Dopamine D1 - drug effects</subject><subject>Receptors, Dopamine D1 - metabolism</subject><subject>Stimulation</subject><subject>striatum</subject><subject>Synaptic cleft</subject><subject>Synthesis</subject><subject>Tetrodotoxin</subject><subject>Toxins</subject><subject>Vesamicol</subject><subject>Vesicular Acetylcholine Transport Proteins - antagonists & inhibitors</subject><subject>Vesicular Acetylcholine Transport Proteins - metabolism</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10E9LwzAYBvAgipvTg19ACl70UJc3TdL2KGP-Y8yLnkuapCwjbWfSKv32Rjs9CObyQvi9Dy8PQueAbyC8-baRN8AY4wdoCjSFmALLD9EUY0LiBFMyQSfebzEGTjkco0lCszTjNJui9fJd2F50pm2itoqcUKa1otRWq0hI3Q1WblprGh35oek22hsfiUZFLgjhdWSasNNFvnNGdH19io4qYb0-288Zer1bviwe4tXz_ePidhVLyiiPVZLmnGRpUkrNCSkrUYHiJK9I-GUE8xQqXqpUVYIxSqUAEAkjnPGMS8XTZIauxtyda9967buiNl5qa0Wj294XhOMMcJ4BBHr5h27b3jXhuqAIQMYSToK6HpV0rfdOV8XOmVq4oQBcfJVchJKL75KDvdgn9mWt1a_8aTWA-Qg-jNXD_0nF03oxRn4CmUOE6Q</recordid><startdate>202202</startdate><enddate>202202</enddate><creator>Muramatsu, Ikunobu</creator><creator>Uwada, Junsuke</creator><creator>Chihara, Kazuyasu</creator><creator>Sada, Kiyonao</creator><creator>Wang, Mao‐Hsien</creator><creator>Yazawa, Takashi</creator><creator>Taniguchi, Takanobu</creator><creator>Ishibashi, Takaharu</creator><creator>Masuoka, Takayoshi</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6881-5391</orcidid></search><sort><creationdate>202202</creationdate><title>Evaluation of radiolabeled acetylcholine synthesis and release in rat striatum</title><author>Muramatsu, Ikunobu ; Uwada, Junsuke ; Chihara, Kazuyasu ; Sada, Kiyonao ; Wang, Mao‐Hsien ; Yazawa, Takashi ; Taniguchi, Takanobu ; Ishibashi, Takaharu ; Masuoka, Takayoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4546-d37962873bce622bfaf1d629f2628520671f6bd7dfa5544ca11a35265686cd673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Accumulation</topic><topic>Acetylcholine</topic><topic>Acetylcholine - biosynthesis</topic><topic>acetylcholine esterase</topic><topic>Acetylcholine receptors (muscarinic)</topic><topic>Acetylcholinesterase</topic><topic>Acetylcholinesterase - metabolism</topic><topic>Animals</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium ions</topic><topic>Central nervous system</topic><topic>Choline</topic><topic>Choline - metabolism</topic><topic>cholinergic release</topic><topic>Cholinergic transmission</topic><topic>Cholinergics</topic><topic>Cholinesterase Inhibitors - pharmacology</topic><topic>Cognition</topic><topic>Cytosol</topic><topic>Depolarization</topic><topic>Dopamine D2 receptors</topic><topic>Electric Stimulation</topic><topic>Electrical stimuli</topic><topic>Esterase</topic><topic>Male</topic><topic>Neostriatum</topic><topic>Neostriatum - metabolism</topic><topic>Potassium chloride</topic><topic>Potassium Chloride - pharmacology</topic><topic>presynaptic modulation</topic><topic>Radiopharmaceuticals</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, Muscarinic M2 - drug effects</topic><topic>Receptor, Muscarinic M2 - metabolism</topic><topic>Receptors, Dopamine D1 - drug effects</topic><topic>Receptors, Dopamine D1 - metabolism</topic><topic>Stimulation</topic><topic>striatum</topic><topic>Synaptic cleft</topic><topic>Synthesis</topic><topic>Tetrodotoxin</topic><topic>Toxins</topic><topic>Vesamicol</topic><topic>Vesicular Acetylcholine Transport Proteins - antagonists & inhibitors</topic><topic>Vesicular Acetylcholine Transport Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muramatsu, Ikunobu</creatorcontrib><creatorcontrib>Uwada, Junsuke</creatorcontrib><creatorcontrib>Chihara, Kazuyasu</creatorcontrib><creatorcontrib>Sada, Kiyonao</creatorcontrib><creatorcontrib>Wang, Mao‐Hsien</creatorcontrib><creatorcontrib>Yazawa, Takashi</creatorcontrib><creatorcontrib>Taniguchi, Takanobu</creatorcontrib><creatorcontrib>Ishibashi, Takaharu</creatorcontrib><creatorcontrib>Masuoka, Takayoshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muramatsu, Ikunobu</au><au>Uwada, Junsuke</au><au>Chihara, Kazuyasu</au><au>Sada, Kiyonao</au><au>Wang, Mao‐Hsien</au><au>Yazawa, Takashi</au><au>Taniguchi, Takanobu</au><au>Ishibashi, Takaharu</au><au>Masuoka, Takayoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of radiolabeled acetylcholine synthesis and release in rat striatum</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2022-02</date><risdate>2022</risdate><volume>160</volume><issue>3</issue><spage>342</spage><epage>355</epage><pages>342-355</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><abstract>Cholinergic transmission underlies higher brain functions such as cognition and movement. To elucidate the process whereby acetylcholine (ACh) release is maintained and regulated in the central nervous system, uptake of [3H]choline and subsequent synthesis and release of [3H]ACh were investigated in rat striatal segments. Incubation with [3H]choline elicited efficient uptake via high‐affinity choline transporter‐1, resulting in accumulation of [3H]choline and [3H]ACh. However, following inhibition of ACh esterase (AChE), incubation with [3H]choline led predominantly to the accumulation of [3H]ACh. Electrical stimulation and KCl depolarization selectively released [3H]ACh but not [3H]choline. [3H]ACh release gradually declined upon repetitive stimulation, whereas the release was reproducible under inhibition of AChE. [3H]ACh release was abolished after treatment with vesamicol, an inhibitor of vesicular ACh transporter. These results suggest that releasable ACh is continually replenished from the cytosol to releasable pools of cholinergic vesicles to maintain cholinergic transmission. [3H]ACh release evoked by electrical stimulation was abolished by tetrodotoxin, but that induced by KCl was largely resistant. ACh release was Ca2+ dependent and exhibited slightly different sensitivities to N‐ and P‐type Ca2+ channel toxins (ω‐conotoxin GVIA and ω‐agatoxin IVA, respectively) between both stimuli. [3H]ACh release was negatively regulated by M2 muscarinic and D2 dopaminergic receptors. The present results suggest that inhibition of AChE within cholinergic neurons and of presynaptic negative regulation of ACh release contributes to maintenance and facilitation of cholinergic transmission, providing a potentially useful clue for the development of therapies for cholinergic dysfunction‐associated disorders, in addition to inhibition of synaptic cleft AChE.
Sustainability of acetylcholine (ACh) release and its regulation in rat striatum were examined. Choline is constitutively supplied into cholinergic terminals through CHT1 and utilized for ACh synthesis. Synthesized ACh is stored in releasable and reserve pools, and excess ACh is degraded by cytosolic AChE. ACh release from releasable pool is negatively regulated by presynaptic M2‐muscarinic (M2R) and D2‐dopaminergic (D2R) receptors. Inhibition of cytosolic AChE and subsequent enhancement of ACh replenishment to releasable pool may contribute to the maintenance and facilitation of cholinergic transmission, in addition to inhibitions of presynaptic negative feedback and synaptic cleft AChE.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>34878648</pmid><doi>10.1111/jnc.15556</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-6881-5391</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Accumulation Acetylcholine Acetylcholine - biosynthesis acetylcholine esterase Acetylcholine receptors (muscarinic) Acetylcholinesterase Acetylcholinesterase - metabolism Animals Calcium Channel Blockers - pharmacology Calcium ions Central nervous system Choline Choline - metabolism cholinergic release Cholinergic transmission Cholinergics Cholinesterase Inhibitors - pharmacology Cognition Cytosol Depolarization Dopamine D2 receptors Electric Stimulation Electrical stimuli Esterase Male Neostriatum Neostriatum - metabolism Potassium chloride Potassium Chloride - pharmacology presynaptic modulation Radiopharmaceuticals Rats Rats, Wistar Receptor, Muscarinic M2 - drug effects Receptor, Muscarinic M2 - metabolism Receptors, Dopamine D1 - drug effects Receptors, Dopamine D1 - metabolism Stimulation striatum Synaptic cleft Synthesis Tetrodotoxin Toxins Vesamicol Vesicular Acetylcholine Transport Proteins - antagonists & inhibitors Vesicular Acetylcholine Transport Proteins - metabolism |
| title | Evaluation of radiolabeled acetylcholine synthesis and release in rat striatum |
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