M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product
The smoke of crack cocaine contains cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). AEME possesses greater neurotoxic potential than cocaine and an additive effect when they are combined. Since atropine prevented AEME-induced neurotoxicity, it has been suggested that its toxi...
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| Veröffentlicht in: | Scientific reports 2015-12, Vol.5 (1), p.17555, Article 17555 |
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| creator | Garcia, Raphael Caio Tamborelli Dati, Livia Mendonça Munhoz Torres, Larissa Helena da Silva, Mariana Aguilera Alencar Udo, Mariana Sayuri Berto Abdalla, Fernando Maurício Francis da Costa, José Luiz Gorjão, Renata Afeche, Solange Castro Yonamine, Mauricio Niswender, Colleen M. Conn, P. Jeffrey Camarini, Rosana Sandoval, Maria Regina Lopes Marcourakis, Tania |
| description | The smoke of crack cocaine contains cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). AEME possesses greater neurotoxic potential than cocaine and an additive effect when they are combined. Since atropine prevented AEME-induced neurotoxicity, it has been suggested that its toxic effects may involve the muscarinic cholinergic receptors (mAChRs). Our aim is to understand the interaction between AEME and mAChRs and how it can lead to neuronal death. Using a rat primary hippocampal cell culture, AEME was shown to cause a concentration-dependent increase on both total [
3
H]inositol phosphate and intracellular calcium and to induce DNA fragmentation after 24 hours of exposure, in line with the activation of caspase-3 previously shown. Additionally, we assessed AEME activity at rat mAChR subtypes 1–5 heterologously expressed in Chinese Hamster Ovary cells. l-[N-methyl-
3
H]scopolamine competition binding showed a preference of AEME for the M
2
subtype; calcium mobilization tests revealed partial agonist effects at M
1
and M
3
and antagonist activity at the remaining subtypes. The selective M
1
and M
3
antagonists and the phospholipase C inhibitor, were able to prevent AEME-induced neurotoxicity, suggesting that the toxicity is due to the partial agonist effect at M
1
and M
3
mAChRs, leading to DNA fragmentation and neuronal death by apoptosis. |
| doi_str_mv | 10.1038/srep17555 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4667193</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4152031561</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-189ac91e39df6ccb936494b737eb7275da72737f0263210e1f9b1d434914c6e03</originalsourceid><addsrcrecordid>eNplkU1P3DAQhq2qqCDg0D9QWeLUigV_xVlfKlWrQpFAXNqz5TiTXaPEDraDmlt_OkYLq63wYWx5nnln7Behz5RcUMKXlynCSOuqqj6gI0ZEtWCcsY9750N0mtIDKatiSlD1CR0yKZkUrDpC_-4oNr7FdxwPU7ImOu8sjmBhzCEmPJgZj30JBsfQA3Ye5w1gD1MMOfx11uUZh65obOY2BrDr4J0HPEDezD2GlCGel2IbrHm5H-ciMyeX8BhDO9l8gg460yc4fd2P0Z-rn79Xvxa399c3qx-3Cyv4Mi_oUhmrKHDVdtLaRnEplGhqXkNTs7pqTYm87giTnFECtFMNbQUXigorgfBj9H2rO07NAK0Fn6Pp9RjdYOKsg3H6_4x3G70OT1pIWVPFi8DZq0AMj1N5mH4IU_RlZk2XlFWkfHhdqK9bysaQijXdrgMl-sUvvfOrsF_2R9qRb-4U4NsWSCXl1xD3Wr5TewZfbKD9</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1812502047</pqid></control><display><type>article</type><title>M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Garcia, Raphael Caio Tamborelli ; Dati, Livia Mendonça Munhoz ; Torres, Larissa Helena ; da Silva, Mariana Aguilera Alencar ; Udo, Mariana Sayuri Berto ; Abdalla, Fernando Maurício Francis ; da Costa, José Luiz ; Gorjão, Renata ; Afeche, Solange Castro ; Yonamine, Mauricio ; Niswender, Colleen M. ; Conn, P. Jeffrey ; Camarini, Rosana ; Sandoval, Maria Regina Lopes ; Marcourakis, Tania</creator><creatorcontrib>Garcia, Raphael Caio Tamborelli ; Dati, Livia Mendonça Munhoz ; Torres, Larissa Helena ; da Silva, Mariana Aguilera Alencar ; Udo, Mariana Sayuri Berto ; Abdalla, Fernando Maurício Francis ; da Costa, José Luiz ; Gorjão, Renata ; Afeche, Solange Castro ; Yonamine, Mauricio ; Niswender, Colleen M. ; Conn, P. Jeffrey ; Camarini, Rosana ; Sandoval, Maria Regina Lopes ; Marcourakis, Tania</creatorcontrib><description>The smoke of crack cocaine contains cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). AEME possesses greater neurotoxic potential than cocaine and an additive effect when they are combined. Since atropine prevented AEME-induced neurotoxicity, it has been suggested that its toxic effects may involve the muscarinic cholinergic receptors (mAChRs). Our aim is to understand the interaction between AEME and mAChRs and how it can lead to neuronal death. Using a rat primary hippocampal cell culture, AEME was shown to cause a concentration-dependent increase on both total [
3
H]inositol phosphate and intracellular calcium and to induce DNA fragmentation after 24 hours of exposure, in line with the activation of caspase-3 previously shown. Additionally, we assessed AEME activity at rat mAChR subtypes 1–5 heterologously expressed in Chinese Hamster Ovary cells. l-[N-methyl-
3
H]scopolamine competition binding showed a preference of AEME for the M
2
subtype; calcium mobilization tests revealed partial agonist effects at M
1
and M
3
and antagonist activity at the remaining subtypes. The selective M
1
and M
3
antagonists and the phospholipase C inhibitor, were able to prevent AEME-induced neurotoxicity, suggesting that the toxicity is due to the partial agonist effect at M
1
and M
3
mAChRs, leading to DNA fragmentation and neuronal death by apoptosis.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep17555</identifier><identifier>PMID: 26626425</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 13/2 ; 631/378/1934 ; 631/378/87 ; 96/34 ; Acetylcholine receptors ; Acetylcholine receptors (muscarinic) ; Animals ; Antagonists ; Apoptosis ; Apoptosis - drug effects ; Atropine ; Calcium ; Calcium (intracellular) ; Calcium mobilization ; Calcium phosphates ; Caspase ; Caspase-3 ; Cell culture ; CHO Cells ; Cocaine ; Cocaine - analogs & derivatives ; Cocaine - toxicity ; Cricetinae ; Cricetulus ; Deoxyribonucleic acid ; DNA ; DNA fragmentation ; DNA Fragmentation - drug effects ; Female ; Hippocampus ; Hippocampus - metabolism ; Hippocampus - pathology ; Humanities and Social Sciences ; Inositol phosphate ; multidisciplinary ; Neurotoxicity ; Neurotoxicity Syndromes - metabolism ; Neurotoxicity Syndromes - pathology ; Neurotoxins - toxicity ; Phospholipase C ; Pyrolysis ; Rats ; Receptor, Muscarinic M1 - metabolism ; Receptor, Muscarinic M3 - metabolism ; Rodents ; Science ; Scopolamine ; Smoke ; Time Factors ; Toxicity</subject><ispartof>Scientific reports, 2015-12, Vol.5 (1), p.17555, Article 17555</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Dec 2015</rights><rights>Copyright © 2015, Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-189ac91e39df6ccb936494b737eb7275da72737f0263210e1f9b1d434914c6e03</citedby><cites>FETCH-LOGICAL-c438t-189ac91e39df6ccb936494b737eb7275da72737f0263210e1f9b1d434914c6e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667193/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667193/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26626425$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Garcia, Raphael Caio Tamborelli</creatorcontrib><creatorcontrib>Dati, Livia Mendonça Munhoz</creatorcontrib><creatorcontrib>Torres, Larissa Helena</creatorcontrib><creatorcontrib>da Silva, Mariana Aguilera Alencar</creatorcontrib><creatorcontrib>Udo, Mariana Sayuri Berto</creatorcontrib><creatorcontrib>Abdalla, Fernando Maurício Francis</creatorcontrib><creatorcontrib>da Costa, José Luiz</creatorcontrib><creatorcontrib>Gorjão, Renata</creatorcontrib><creatorcontrib>Afeche, Solange Castro</creatorcontrib><creatorcontrib>Yonamine, Mauricio</creatorcontrib><creatorcontrib>Niswender, Colleen M.</creatorcontrib><creatorcontrib>Conn, P. Jeffrey</creatorcontrib><creatorcontrib>Camarini, Rosana</creatorcontrib><creatorcontrib>Sandoval, Maria Regina Lopes</creatorcontrib><creatorcontrib>Marcourakis, Tania</creatorcontrib><title>M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The smoke of crack cocaine contains cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). AEME possesses greater neurotoxic potential than cocaine and an additive effect when they are combined. Since atropine prevented AEME-induced neurotoxicity, it has been suggested that its toxic effects may involve the muscarinic cholinergic receptors (mAChRs). Our aim is to understand the interaction between AEME and mAChRs and how it can lead to neuronal death. Using a rat primary hippocampal cell culture, AEME was shown to cause a concentration-dependent increase on both total [
3
H]inositol phosphate and intracellular calcium and to induce DNA fragmentation after 24 hours of exposure, in line with the activation of caspase-3 previously shown. Additionally, we assessed AEME activity at rat mAChR subtypes 1–5 heterologously expressed in Chinese Hamster Ovary cells. l-[N-methyl-
3
H]scopolamine competition binding showed a preference of AEME for the M
2
subtype; calcium mobilization tests revealed partial agonist effects at M
1
and M
3
and antagonist activity at the remaining subtypes. The selective M
1
and M
3
antagonists and the phospholipase C inhibitor, were able to prevent AEME-induced neurotoxicity, suggesting that the toxicity is due to the partial agonist effect at M
1
and M
3
mAChRs, leading to DNA fragmentation and neuronal death by apoptosis.</description><subject>13/106</subject><subject>13/2</subject><subject>631/378/1934</subject><subject>631/378/87</subject><subject>96/34</subject><subject>Acetylcholine receptors</subject><subject>Acetylcholine receptors (muscarinic)</subject><subject>Animals</subject><subject>Antagonists</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Atropine</subject><subject>Calcium</subject><subject>Calcium (intracellular)</subject><subject>Calcium mobilization</subject><subject>Calcium phosphates</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cell culture</subject><subject>CHO Cells</subject><subject>Cocaine</subject><subject>Cocaine - analogs & derivatives</subject><subject>Cocaine - toxicity</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA fragmentation</subject><subject>DNA Fragmentation - drug effects</subject><subject>Female</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Humanities and Social Sciences</subject><subject>Inositol phosphate</subject><subject>multidisciplinary</subject><subject>Neurotoxicity</subject><subject>Neurotoxicity Syndromes - metabolism</subject><subject>Neurotoxicity Syndromes - pathology</subject><subject>Neurotoxins - toxicity</subject><subject>Phospholipase C</subject><subject>Pyrolysis</subject><subject>Rats</subject><subject>Receptor, Muscarinic M1 - metabolism</subject><subject>Receptor, Muscarinic M3 - metabolism</subject><subject>Rodents</subject><subject>Science</subject><subject>Scopolamine</subject><subject>Smoke</subject><subject>Time Factors</subject><subject>Toxicity</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkU1P3DAQhq2qqCDg0D9QWeLUigV_xVlfKlWrQpFAXNqz5TiTXaPEDraDmlt_OkYLq63wYWx5nnln7Behz5RcUMKXlynCSOuqqj6gI0ZEtWCcsY9750N0mtIDKatiSlD1CR0yKZkUrDpC_-4oNr7FdxwPU7ImOu8sjmBhzCEmPJgZj30JBsfQA3Ye5w1gD1MMOfx11uUZh65obOY2BrDr4J0HPEDezD2GlCGel2IbrHm5H-ciMyeX8BhDO9l8gg460yc4fd2P0Z-rn79Xvxa399c3qx-3Cyv4Mi_oUhmrKHDVdtLaRnEplGhqXkNTs7pqTYm87giTnFECtFMNbQUXigorgfBj9H2rO07NAK0Fn6Pp9RjdYOKsg3H6_4x3G70OT1pIWVPFi8DZq0AMj1N5mH4IU_RlZk2XlFWkfHhdqK9bysaQijXdrgMl-sUvvfOrsF_2R9qRb-4U4NsWSCXl1xD3Wr5TewZfbKD9</recordid><startdate>20151202</startdate><enddate>20151202</enddate><creator>Garcia, Raphael Caio Tamborelli</creator><creator>Dati, Livia Mendonça Munhoz</creator><creator>Torres, Larissa Helena</creator><creator>da Silva, Mariana Aguilera Alencar</creator><creator>Udo, Mariana Sayuri Berto</creator><creator>Abdalla, Fernando Maurício Francis</creator><creator>da Costa, José Luiz</creator><creator>Gorjão, Renata</creator><creator>Afeche, Solange Castro</creator><creator>Yonamine, Mauricio</creator><creator>Niswender, Colleen M.</creator><creator>Conn, P. 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Jeffrey ; Camarini, Rosana ; Sandoval, Maria Regina Lopes ; Marcourakis, Tania</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-189ac91e39df6ccb936494b737eb7275da72737f0263210e1f9b1d434914c6e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>13/106</topic><topic>13/2</topic><topic>631/378/1934</topic><topic>631/378/87</topic><topic>96/34</topic><topic>Acetylcholine receptors</topic><topic>Acetylcholine receptors (muscarinic)</topic><topic>Animals</topic><topic>Antagonists</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Atropine</topic><topic>Calcium</topic><topic>Calcium (intracellular)</topic><topic>Calcium mobilization</topic><topic>Calcium phosphates</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Cell culture</topic><topic>CHO Cells</topic><topic>Cocaine</topic><topic>Cocaine - analogs & derivatives</topic><topic>Cocaine - toxicity</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA fragmentation</topic><topic>DNA Fragmentation - drug effects</topic><topic>Female</topic><topic>Hippocampus</topic><topic>Hippocampus - metabolism</topic><topic>Hippocampus - pathology</topic><topic>Humanities and Social Sciences</topic><topic>Inositol phosphate</topic><topic>multidisciplinary</topic><topic>Neurotoxicity</topic><topic>Neurotoxicity Syndromes - metabolism</topic><topic>Neurotoxicity Syndromes - pathology</topic><topic>Neurotoxins - toxicity</topic><topic>Phospholipase C</topic><topic>Pyrolysis</topic><topic>Rats</topic><topic>Receptor, Muscarinic M1 - metabolism</topic><topic>Receptor, Muscarinic M3 - metabolism</topic><topic>Rodents</topic><topic>Science</topic><topic>Scopolamine</topic><topic>Smoke</topic><topic>Time Factors</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garcia, Raphael Caio Tamborelli</creatorcontrib><creatorcontrib>Dati, Livia Mendonça Munhoz</creatorcontrib><creatorcontrib>Torres, Larissa Helena</creatorcontrib><creatorcontrib>da Silva, Mariana Aguilera Alencar</creatorcontrib><creatorcontrib>Udo, Mariana Sayuri Berto</creatorcontrib><creatorcontrib>Abdalla, Fernando Maurício Francis</creatorcontrib><creatorcontrib>da Costa, José Luiz</creatorcontrib><creatorcontrib>Gorjão, Renata</creatorcontrib><creatorcontrib>Afeche, Solange Castro</creatorcontrib><creatorcontrib>Yonamine, Mauricio</creatorcontrib><creatorcontrib>Niswender, Colleen M.</creatorcontrib><creatorcontrib>Conn, P. Jeffrey</creatorcontrib><creatorcontrib>Camarini, Rosana</creatorcontrib><creatorcontrib>Sandoval, Maria Regina Lopes</creatorcontrib><creatorcontrib>Marcourakis, Tania</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database (ProQuest)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garcia, Raphael Caio Tamborelli</au><au>Dati, Livia Mendonça Munhoz</au><au>Torres, Larissa Helena</au><au>da Silva, Mariana Aguilera Alencar</au><au>Udo, Mariana Sayuri Berto</au><au>Abdalla, Fernando Maurício Francis</au><au>da Costa, José Luiz</au><au>Gorjão, Renata</au><au>Afeche, Solange Castro</au><au>Yonamine, Mauricio</au><au>Niswender, Colleen M.</au><au>Conn, P. Jeffrey</au><au>Camarini, Rosana</au><au>Sandoval, Maria Regina Lopes</au><au>Marcourakis, Tania</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2015-12-02</date><risdate>2015</risdate><volume>5</volume><issue>1</issue><spage>17555</spage><pages>17555-</pages><artnum>17555</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The smoke of crack cocaine contains cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). AEME possesses greater neurotoxic potential than cocaine and an additive effect when they are combined. Since atropine prevented AEME-induced neurotoxicity, it has been suggested that its toxic effects may involve the muscarinic cholinergic receptors (mAChRs). Our aim is to understand the interaction between AEME and mAChRs and how it can lead to neuronal death. Using a rat primary hippocampal cell culture, AEME was shown to cause a concentration-dependent increase on both total [
3
H]inositol phosphate and intracellular calcium and to induce DNA fragmentation after 24 hours of exposure, in line with the activation of caspase-3 previously shown. Additionally, we assessed AEME activity at rat mAChR subtypes 1–5 heterologously expressed in Chinese Hamster Ovary cells. l-[N-methyl-
3
H]scopolamine competition binding showed a preference of AEME for the M
2
subtype; calcium mobilization tests revealed partial agonist effects at M
1
and M
3
and antagonist activity at the remaining subtypes. The selective M
1
and M
3
antagonists and the phospholipase C inhibitor, were able to prevent AEME-induced neurotoxicity, suggesting that the toxicity is due to the partial agonist effect at M
1
and M
3
mAChRs, leading to DNA fragmentation and neuronal death by apoptosis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26626425</pmid><doi>10.1038/srep17555</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2015-12, Vol.5 (1), p.17555, Article 17555 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4667193 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 13/106 13/2 631/378/1934 631/378/87 96/34 Acetylcholine receptors Acetylcholine receptors (muscarinic) Animals Antagonists Apoptosis Apoptosis - drug effects Atropine Calcium Calcium (intracellular) Calcium mobilization Calcium phosphates Caspase Caspase-3 Cell culture CHO Cells Cocaine Cocaine - analogs & derivatives Cocaine - toxicity Cricetinae Cricetulus Deoxyribonucleic acid DNA DNA fragmentation DNA Fragmentation - drug effects Female Hippocampus Hippocampus - metabolism Hippocampus - pathology Humanities and Social Sciences Inositol phosphate multidisciplinary Neurotoxicity Neurotoxicity Syndromes - metabolism Neurotoxicity Syndromes - pathology Neurotoxins - toxicity Phospholipase C Pyrolysis Rats Receptor, Muscarinic M1 - metabolism Receptor, Muscarinic M3 - metabolism Rodents Science Scopolamine Smoke Time Factors Toxicity |
| title | M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T11%3A20%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=M1%20and%20M3%20muscarinic%20receptors%20may%20play%20a%20role%20in%20the%20neurotoxicity%20of%20anhydroecgonine%20methyl%20ester,%20a%20cocaine%20pyrolysis%20product&rft.jtitle=Scientific%20reports&rft.au=Garcia,%20Raphael%20Caio%20Tamborelli&rft.date=2015-12-02&rft.volume=5&rft.issue=1&rft.spage=17555&rft.pages=17555-&rft.artnum=17555&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/srep17555&rft_dat=%3Cproquest_pubme%3E4152031561%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1812502047&rft_id=info:pmid/26626425&rfr_iscdi=true |