Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype
Muscarinic acetylcholine receptors consist of five distinct subtypes and have been important targets for drug development. In the periphery, muscarinic acetylcholine receptors mediate cholinergic signals to autonomic organs, but specific physiological functions of each subtype remain poorly elucidat...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2000-08, Vol.97 (17), p.9579-9584 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 9584 |
|---|---|
| container_issue | 17 |
| container_start_page | 9579 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 97 |
| creator | Matsui, M Motomura, D Karasawa, H Fujikawa, T Jiang, J Komiya, Y Takahashi, S Taketo, M M |
| description | Muscarinic acetylcholine receptors consist of five distinct subtypes and have been important targets for drug development. In the periphery, muscarinic acetylcholine receptors mediate cholinergic signals to autonomic organs, but specific physiological functions of each subtype remain poorly elucidated. Here, we have constructed and analyzed mutant mice lacking the M 3 receptor and have demonstrated that this subtype plays key roles in salivary secretion, pupillary constriction, and bladder detrusor contractions. However, M 3 -mediated signals in digestive and reproductive organs are dispensable, likely because of redundant mechanisms through other muscarinic acetylcholine receptor subtypes or other mediators. In addition, we have found prominent urinary retention only in the male, which indicates a considerable sex difference in the micturition mechanism. Accordingly, this mutant mouse should provide a useful animal model for investigation of human diseases that are affected in the peripheral cholinergic functions. |
| doi_str_mv | 10.1073/pnas.97.17.9579 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pnas_</sourceid><recordid>TN_cdi_proquest_journals_201369496</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71750282</sourcerecordid><originalsourceid>FETCH-LOGICAL-p257t-ffb76857f25ac87b55ba3d7ddc9ebe49747a24ba767ea94e84b2a2bc6e5c2b53</originalsourceid><addsrcrecordid>eNp9kc2PFCEQxYnRuOPo2ZshHvTUI01D0yRezMavZDde9k6Arp5hZaDlwzh3_3BR183qwRNUvR-VRz2EnvZk1xMxvFqDzjspdr3YSS7kPbTpiey7kUlyH20IoaKbGGVn6FHO14QQySfyEJ01iDFK2QZ9v6y-uNUDXmqwxcWgPZ5hAVsydgGvkNx6gNS6upYY4tFZHNNeh19yqwB7bT-7sMfHmq1OLjRCWygnbw_RuwA4gYW1xIT30KqlXcoB8OWAczXltMJj9GDRPsOTm3OLrt69vTr_0F18ev_x_M1Ft1IuSrcsRowTFwvl2k7CcG70MIt5thIMMCmY0JQZLUYBWjKYmKGaGjsCt9TwYYte_x67VnOE2UIo7V9qTe6o00lF7dTfSnAHtY9fVT_KtuwtenHzPMUvFXJRR5cteK8DxJqV6AUndKINfP4PeB1raovNipJ-GCWTY4Oe3TVz6-JPNHeAlvGtLIXqhfqZdQNe_hdQS_W-wLcy_AC9mK2w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>201369496</pqid></control><display><type>article</type><title>Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype</title><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Matsui, M ; Motomura, D ; Karasawa, H ; Fujikawa, T ; Jiang, J ; Komiya, Y ; Takahashi, S ; Taketo, M M</creator><creatorcontrib>Matsui, M ; Motomura, D ; Karasawa, H ; Fujikawa, T ; Jiang, J ; Komiya, Y ; Takahashi, S ; Taketo, M M</creatorcontrib><description>Muscarinic acetylcholine receptors consist of five distinct subtypes and have been important targets for drug development. In the periphery, muscarinic acetylcholine receptors mediate cholinergic signals to autonomic organs, but specific physiological functions of each subtype remain poorly elucidated. Here, we have constructed and analyzed mutant mice lacking the M 3 receptor and have demonstrated that this subtype plays key roles in salivary secretion, pupillary constriction, and bladder detrusor contractions. However, M 3 -mediated signals in digestive and reproductive organs are dispensable, likely because of redundant mechanisms through other muscarinic acetylcholine receptor subtypes or other mediators. In addition, we have found prominent urinary retention only in the male, which indicates a considerable sex difference in the micturition mechanism. Accordingly, this mutant mouse should provide a useful animal model for investigation of human diseases that are affected in the peripheral cholinergic functions.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.97.17.9579</identifier><identifier>PMID: 10944224</identifier><language>eng</language><publisher>United States: National Acad Sciences</publisher><subject>Animals ; Biological Sciences ; Body Weight ; Carbachol - pharmacology ; Digestive System - physiopathology ; Digestive System Abnormalities ; Female ; Fertility - genetics ; Gene Deletion ; Gene Targeting ; Growth Disorders - genetics ; Growth Disorders - metabolism ; Growth Disorders - physiopathology ; Heterozygote ; Homozygote ; Male ; Medical research ; Mice ; Mice, Knockout ; Muscle Contraction ; Muscle, Smooth - physiopathology ; Mutation ; Pharmacology ; Phenotype ; Pilocarpine - pharmacology ; Pupil - drug effects ; Pupil Disorders - metabolism ; Pupil Disorders - physiopathology ; Receptor, Muscarinic M1 ; Receptor, Muscarinic M3 ; Receptors, Muscarinic - deficiency ; Receptors, Muscarinic - genetics ; Receptors, Muscarinic - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Saliva - metabolism ; Salivary Glands - drug effects ; Salivary Glands - metabolism ; Salivary Glands - physiopathology ; Sex Characteristics ; Sexes ; Urinary Bladder - abnormalities ; Urinary Bladder - metabolism ; Urinary Bladder - physiopathology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2000-08, Vol.97 (17), p.9579-9584</ispartof><rights>Copyright National Academy of Sciences Aug 15, 2000</rights><rights>Copyright © 2000, The National Academy of Sciences 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/97/17.cover.gif</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC16907/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC16907/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10944224$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsui, M</creatorcontrib><creatorcontrib>Motomura, D</creatorcontrib><creatorcontrib>Karasawa, H</creatorcontrib><creatorcontrib>Fujikawa, T</creatorcontrib><creatorcontrib>Jiang, J</creatorcontrib><creatorcontrib>Komiya, Y</creatorcontrib><creatorcontrib>Takahashi, S</creatorcontrib><creatorcontrib>Taketo, M M</creatorcontrib><title>Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Muscarinic acetylcholine receptors consist of five distinct subtypes and have been important targets for drug development. In the periphery, muscarinic acetylcholine receptors mediate cholinergic signals to autonomic organs, but specific physiological functions of each subtype remain poorly elucidated. Here, we have constructed and analyzed mutant mice lacking the M 3 receptor and have demonstrated that this subtype plays key roles in salivary secretion, pupillary constriction, and bladder detrusor contractions. However, M 3 -mediated signals in digestive and reproductive organs are dispensable, likely because of redundant mechanisms through other muscarinic acetylcholine receptor subtypes or other mediators. In addition, we have found prominent urinary retention only in the male, which indicates a considerable sex difference in the micturition mechanism. Accordingly, this mutant mouse should provide a useful animal model for investigation of human diseases that are affected in the peripheral cholinergic functions.</description><subject>Animals</subject><subject>Biological Sciences</subject><subject>Body Weight</subject><subject>Carbachol - pharmacology</subject><subject>Digestive System - physiopathology</subject><subject>Digestive System Abnormalities</subject><subject>Female</subject><subject>Fertility - genetics</subject><subject>Gene Deletion</subject><subject>Gene Targeting</subject><subject>Growth Disorders - genetics</subject><subject>Growth Disorders - metabolism</subject><subject>Growth Disorders - physiopathology</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Male</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Muscle Contraction</subject><subject>Muscle, Smooth - physiopathology</subject><subject>Mutation</subject><subject>Pharmacology</subject><subject>Phenotype</subject><subject>Pilocarpine - pharmacology</subject><subject>Pupil - drug effects</subject><subject>Pupil Disorders - metabolism</subject><subject>Pupil Disorders - physiopathology</subject><subject>Receptor, Muscarinic M1</subject><subject>Receptor, Muscarinic M3</subject><subject>Receptors, Muscarinic - deficiency</subject><subject>Receptors, Muscarinic - genetics</subject><subject>Receptors, Muscarinic - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Saliva - metabolism</subject><subject>Salivary Glands - drug effects</subject><subject>Salivary Glands - metabolism</subject><subject>Salivary Glands - physiopathology</subject><subject>Sex Characteristics</subject><subject>Sexes</subject><subject>Urinary Bladder - abnormalities</subject><subject>Urinary Bladder - metabolism</subject><subject>Urinary Bladder - physiopathology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2PFCEQxYnRuOPo2ZshHvTUI01D0yRezMavZDde9k6Arp5hZaDlwzh3_3BR183qwRNUvR-VRz2EnvZk1xMxvFqDzjspdr3YSS7kPbTpiey7kUlyH20IoaKbGGVn6FHO14QQySfyEJ01iDFK2QZ9v6y-uNUDXmqwxcWgPZ5hAVsydgGvkNx6gNS6upYY4tFZHNNeh19yqwB7bT-7sMfHmq1OLjRCWygnbw_RuwA4gYW1xIT30KqlXcoB8OWAczXltMJj9GDRPsOTm3OLrt69vTr_0F18ev_x_M1Ft1IuSrcsRowTFwvl2k7CcG70MIt5thIMMCmY0JQZLUYBWjKYmKGaGjsCt9TwYYte_x67VnOE2UIo7V9qTe6o00lF7dTfSnAHtY9fVT_KtuwtenHzPMUvFXJRR5cteK8DxJqV6AUndKINfP4PeB1raovNipJ-GCWTY4Oe3TVz6-JPNHeAlvGtLIXqhfqZdQNe_hdQS_W-wLcy_AC9mK2w</recordid><startdate>20000815</startdate><enddate>20000815</enddate><creator>Matsui, M</creator><creator>Motomura, D</creator><creator>Karasawa, H</creator><creator>Fujikawa, T</creator><creator>Jiang, J</creator><creator>Komiya, Y</creator><creator>Takahashi, S</creator><creator>Taketo, M M</creator><general>National Acad Sciences</general><general>National Academy of Sciences</general><general>The National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20000815</creationdate><title>Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype</title><author>Matsui, M ; Motomura, D ; Karasawa, H ; Fujikawa, T ; Jiang, J ; Komiya, Y ; Takahashi, S ; Taketo, M M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p257t-ffb76857f25ac87b55ba3d7ddc9ebe49747a24ba767ea94e84b2a2bc6e5c2b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Biological Sciences</topic><topic>Body Weight</topic><topic>Carbachol - pharmacology</topic><topic>Digestive System - physiopathology</topic><topic>Digestive System Abnormalities</topic><topic>Female</topic><topic>Fertility - genetics</topic><topic>Gene Deletion</topic><topic>Gene Targeting</topic><topic>Growth Disorders - genetics</topic><topic>Growth Disorders - metabolism</topic><topic>Growth Disorders - physiopathology</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Male</topic><topic>Medical research</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Muscle Contraction</topic><topic>Muscle, Smooth - physiopathology</topic><topic>Mutation</topic><topic>Pharmacology</topic><topic>Phenotype</topic><topic>Pilocarpine - pharmacology</topic><topic>Pupil - drug effects</topic><topic>Pupil Disorders - metabolism</topic><topic>Pupil Disorders - physiopathology</topic><topic>Receptor, Muscarinic M1</topic><topic>Receptor, Muscarinic M3</topic><topic>Receptors, Muscarinic - deficiency</topic><topic>Receptors, Muscarinic - genetics</topic><topic>Receptors, Muscarinic - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Saliva - metabolism</topic><topic>Salivary Glands - drug effects</topic><topic>Salivary Glands - metabolism</topic><topic>Salivary Glands - physiopathology</topic><topic>Sex Characteristics</topic><topic>Sexes</topic><topic>Urinary Bladder - abnormalities</topic><topic>Urinary Bladder - metabolism</topic><topic>Urinary Bladder - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matsui, M</creatorcontrib><creatorcontrib>Motomura, D</creatorcontrib><creatorcontrib>Karasawa, H</creatorcontrib><creatorcontrib>Fujikawa, T</creatorcontrib><creatorcontrib>Jiang, J</creatorcontrib><creatorcontrib>Komiya, Y</creatorcontrib><creatorcontrib>Takahashi, S</creatorcontrib><creatorcontrib>Taketo, M M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors 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>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matsui, M</au><au>Motomura, D</au><au>Karasawa, H</au><au>Fujikawa, T</au><au>Jiang, J</au><au>Komiya, Y</au><au>Takahashi, S</au><au>Taketo, M M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2000-08-15</date><risdate>2000</risdate><volume>97</volume><issue>17</issue><spage>9579</spage><epage>9584</epage><pages>9579-9584</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Muscarinic acetylcholine receptors consist of five distinct subtypes and have been important targets for drug development. In the periphery, muscarinic acetylcholine receptors mediate cholinergic signals to autonomic organs, but specific physiological functions of each subtype remain poorly elucidated. Here, we have constructed and analyzed mutant mice lacking the M 3 receptor and have demonstrated that this subtype plays key roles in salivary secretion, pupillary constriction, and bladder detrusor contractions. However, M 3 -mediated signals in digestive and reproductive organs are dispensable, likely because of redundant mechanisms through other muscarinic acetylcholine receptor subtypes or other mediators. In addition, we have found prominent urinary retention only in the male, which indicates a considerable sex difference in the micturition mechanism. Accordingly, this mutant mouse should provide a useful animal model for investigation of human diseases that are affected in the peripheral cholinergic functions.</abstract><cop>United States</cop><pub>National Acad Sciences</pub><pmid>10944224</pmid><doi>10.1073/pnas.97.17.9579</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2000-08, Vol.97 (17), p.9579-9584 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_proquest_journals_201369496 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Biological Sciences Body Weight Carbachol - pharmacology Digestive System - physiopathology Digestive System Abnormalities Female Fertility - genetics Gene Deletion Gene Targeting Growth Disorders - genetics Growth Disorders - metabolism Growth Disorders - physiopathology Heterozygote Homozygote Male Medical research Mice Mice, Knockout Muscle Contraction Muscle, Smooth - physiopathology Mutation Pharmacology Phenotype Pilocarpine - pharmacology Pupil - drug effects Pupil Disorders - metabolism Pupil Disorders - physiopathology Receptor, Muscarinic M1 Receptor, Muscarinic M3 Receptors, Muscarinic - deficiency Receptors, Muscarinic - genetics Receptors, Muscarinic - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Saliva - metabolism Salivary Glands - drug effects Salivary Glands - metabolism Salivary Glands - physiopathology Sex Characteristics Sexes Urinary Bladder - abnormalities Urinary Bladder - metabolism Urinary Bladder - physiopathology |
| title | Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T23%3A22%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pnas_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multiple%20functional%20defects%20in%20peripheral%20autonomic%20organs%20in%20mice%20lacking%20muscarinic%20acetylcholine%20receptor%20gene%20for%20the%20M3%20subtype&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Matsui,%20M&rft.date=2000-08-15&rft.volume=97&rft.issue=17&rft.spage=9579&rft.epage=9584&rft.pages=9579-9584&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.97.17.9579&rft_dat=%3Cproquest_pnas_%3E71750282%3C/proquest_pnas_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201369496&rft_id=info:pmid/10944224&rfr_iscdi=true |