Biochemical Characterization of a Novel Channel-Activating Site on Nicotinic Acetylcholine Receptors
Abstract We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine and several structurally related compounds with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligand-induced ion flux into nAChR-rich membran...
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| Veröffentlicht in: | Journal of receptor research 1993, Vol.13 (1-4), p.393-412 |
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| container_title | Journal of receptor research |
| container_volume | 13 |
| creator | Schrattenholz, Andre Coban, Thomas Schröder, Bernd Okonjo, Kehinde O. Kuhlmann, Jürgen Pereira, Edna F. Albuquerque, Edson X. Maelicke, Alfred |
| description | Abstract
We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine and several structurally related compounds with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligand-induced ion flux into nAChR-rich membrane vesicles, direct binding studies and photoaffinity labeling. (-)Physostigmine acts as a channel-activating ligand at low concentrations and as a direct channel blocker at elevated concentrations. Channel activation is not inhibited by desensitizing concentrations of ACh or ACh-competitive ligands (including α-bungarotoxin and D-tubocurarine) but is inhibited by antibody FK1 and several other compounds. From photoaffinity labeling using tritiated physostigmine and mapping of the epitope for the Phy-competitive antibody FK1, the binding site for physostigmine is located within the a-subunit of the Torpedo nAChR and is distinct from the acetylcholine binding site. Our data suggest a second pathway of nAChR channel activation that may function physiologically as an allosteric control of receptor activity. |
| doi_str_mv | 10.3109/10799899309073669 |
| format | Article |
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We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine and several structurally related compounds with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligand-induced ion flux into nAChR-rich membrane vesicles, direct binding studies and photoaffinity labeling. (-)Physostigmine acts as a channel-activating ligand at low concentrations and as a direct channel blocker at elevated concentrations. Channel activation is not inhibited by desensitizing concentrations of ACh or ACh-competitive ligands (including α-bungarotoxin and D-tubocurarine) but is inhibited by antibody FK1 and several other compounds. From photoaffinity labeling using tritiated physostigmine and mapping of the epitope for the Phy-competitive antibody FK1, the binding site for physostigmine is located within the a-subunit of the Torpedo nAChR and is distinct from the acetylcholine binding site. Our data suggest a second pathway of nAChR channel activation that may function physiologically as an allosteric control of receptor activity.</description><identifier>ISSN: 1079-9893</identifier><identifier>ISSN: 0197-5110</identifier><identifier>EISSN: 1532-4281</identifier><identifier>DOI: 10.3109/10799899309073669</identifier><identifier>PMID: 7680720</identifier><identifier>CODEN: JRERDM</identifier><language>eng</language><publisher>Basel: Informa UK Ltd</publisher><subject>Amino Acid Sequence ; Animals ; Biological and medical sciences ; Cell receptors ; Cell structures and functions ; Fundamental and applied biological sciences. Psychology ; In Vitro Techniques ; Ion Channels - drug effects ; Molecular and cellular biology ; Molecular Sequence Data ; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine) ; Physostigmine - metabolism ; Physostigmine - pharmacology ; Receptors, Nicotinic - drug effects ; Receptors, Nicotinic - metabolism ; Torpedo</subject><ispartof>Journal of receptor research, 1993, Vol.13 (1-4), p.393-412</ispartof><rights>1993 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 1993</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-c9637b33e2320e6ceaabb2761ee7365290a82fdb4bad9a549917d3cd3d49ff403</citedby><cites>FETCH-LOGICAL-c430t-c9637b33e2320e6ceaabb2761ee7365290a82fdb4bad9a549917d3cd3d49ff403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.3109/10799899309073669$$EPDF$$P50$$Ginformahealthcare$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.3109/10799899309073669$$EHTML$$P50$$Ginformahealthcare$$H</linktohtml><link.rule.ids>309,310,314,776,780,785,786,4009,4035,4036,23910,23911,25119,27902,27903,27904,59624,60413,61198,61233,61379,61414</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4612408$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7680720$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schrattenholz, Andre</creatorcontrib><creatorcontrib>Coban, Thomas</creatorcontrib><creatorcontrib>Schröder, Bernd</creatorcontrib><creatorcontrib>Okonjo, Kehinde O.</creatorcontrib><creatorcontrib>Kuhlmann, Jürgen</creatorcontrib><creatorcontrib>Pereira, Edna F.</creatorcontrib><creatorcontrib>Albuquerque, Edson X.</creatorcontrib><creatorcontrib>Maelicke, Alfred</creatorcontrib><title>Biochemical Characterization of a Novel Channel-Activating Site on Nicotinic Acetylcholine Receptors</title><title>Journal of receptor research</title><addtitle>J Recept Res</addtitle><description>Abstract
We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine and several structurally related compounds with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligand-induced ion flux into nAChR-rich membrane vesicles, direct binding studies and photoaffinity labeling. (-)Physostigmine acts as a channel-activating ligand at low concentrations and as a direct channel blocker at elevated concentrations. Channel activation is not inhibited by desensitizing concentrations of ACh or ACh-competitive ligands (including α-bungarotoxin and D-tubocurarine) but is inhibited by antibody FK1 and several other compounds. From photoaffinity labeling using tritiated physostigmine and mapping of the epitope for the Phy-competitive antibody FK1, the binding site for physostigmine is located within the a-subunit of the Torpedo nAChR and is distinct from the acetylcholine binding site. Our data suggest a second pathway of nAChR channel activation that may function physiologically as an allosteric control of receptor activity.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>In Vitro Techniques</subject><subject>Ion Channels - drug effects</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine)</subject><subject>Physostigmine - metabolism</subject><subject>Physostigmine - pharmacology</subject><subject>Receptors, Nicotinic - drug effects</subject><subject>Receptors, Nicotinic - metabolism</subject><subject>Torpedo</subject><issn>1079-9893</issn><issn>0197-5110</issn><issn>1532-4281</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kFtv1DAQhS0EKm3hB_CAlAfEW8CXbBwLXpZVuUhVkbg8R5PJhLhy7MX2Fi2_HsMulRBSn8aa850Zz2HsieAvlODmpeDamM4YxQ3Xqm3NPXYqVkrWjezE_fIuel0A9ZCdpXTNuTBa8BN2otuOa8lP2fjGBpxpsQiu2swQATNF-xOyDb4KUwXVVbihP5r35Oo1ZntTVP-t-mwzVYW6shhKw2K1Rsp7h3Nw1lP1iZC2OcT0iD2YwCV6fKzn7Ovbiy-b9_Xlx3cfNuvLGhvFc42mVXpQiqSSnFokgGGQuhVE5biVNBw6OY1DM8BoYNUYI_SocFRjY6ap4eqcPT_M3cbwfUcp94tNSM6Bp7BLvV61QvJOFlAcQIwhpUhTv412gbjvBe9_J9v_l2zxPD0O3w0LjbeOY5RFf3bUIZUwpwgebbrFmrK64V3BXh8w66cQF_gRohv7DHsX4l-PuusXr_6xzwQuzwiR-uuwi77Ee8cNvwB4labT</recordid><startdate>1993</startdate><enddate>1993</enddate><creator>Schrattenholz, Andre</creator><creator>Coban, Thomas</creator><creator>Schröder, Bernd</creator><creator>Okonjo, Kehinde O.</creator><creator>Kuhlmann, Jürgen</creator><creator>Pereira, Edna F.</creator><creator>Albuquerque, Edson X.</creator><creator>Maelicke, Alfred</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><general>Dekker</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>1993</creationdate><title>Biochemical Characterization of a Novel Channel-Activating Site on Nicotinic Acetylcholine Receptors</title><author>Schrattenholz, Andre ; Coban, Thomas ; Schröder, Bernd ; Okonjo, Kehinde O. ; Kuhlmann, Jürgen ; Pereira, Edna F. ; Albuquerque, Edson X. ; Maelicke, Alfred</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-c9637b33e2320e6ceaabb2761ee7365290a82fdb4bad9a549917d3cd3d49ff403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>In Vitro Techniques</topic><topic>Ion Channels - drug effects</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine)</topic><topic>Physostigmine - metabolism</topic><topic>Physostigmine - pharmacology</topic><topic>Receptors, Nicotinic - drug effects</topic><topic>Receptors, Nicotinic - metabolism</topic><topic>Torpedo</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schrattenholz, Andre</creatorcontrib><creatorcontrib>Coban, Thomas</creatorcontrib><creatorcontrib>Schröder, Bernd</creatorcontrib><creatorcontrib>Okonjo, Kehinde O.</creatorcontrib><creatorcontrib>Kuhlmann, Jürgen</creatorcontrib><creatorcontrib>Pereira, Edna F.</creatorcontrib><creatorcontrib>Albuquerque, Edson X.</creatorcontrib><creatorcontrib>Maelicke, Alfred</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of receptor research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schrattenholz, Andre</au><au>Coban, Thomas</au><au>Schröder, Bernd</au><au>Okonjo, Kehinde O.</au><au>Kuhlmann, Jürgen</au><au>Pereira, Edna F.</au><au>Albuquerque, Edson X.</au><au>Maelicke, Alfred</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biochemical Characterization of a Novel Channel-Activating Site on Nicotinic Acetylcholine Receptors</atitle><jtitle>Journal of receptor research</jtitle><addtitle>J Recept Res</addtitle><date>1993</date><risdate>1993</risdate><volume>13</volume><issue>1-4</issue><spage>393</spage><epage>412</epage><pages>393-412</pages><issn>1079-9893</issn><issn>0197-5110</issn><eissn>1532-4281</eissn><coden>JRERDM</coden><abstract>Abstract
We have studied the interaction of the reversible acetylcholine esterase inhibitor (-)physostigmine and several structurally related compounds with the nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata electric tissue by means of ligand-induced ion flux into nAChR-rich membrane vesicles, direct binding studies and photoaffinity labeling. (-)Physostigmine acts as a channel-activating ligand at low concentrations and as a direct channel blocker at elevated concentrations. Channel activation is not inhibited by desensitizing concentrations of ACh or ACh-competitive ligands (including α-bungarotoxin and D-tubocurarine) but is inhibited by antibody FK1 and several other compounds. From photoaffinity labeling using tritiated physostigmine and mapping of the epitope for the Phy-competitive antibody FK1, the binding site for physostigmine is located within the a-subunit of the Torpedo nAChR and is distinct from the acetylcholine binding site. Our data suggest a second pathway of nAChR channel activation that may function physiologically as an allosteric control of receptor activity.</abstract><cop>Basel</cop><cop>Hong Kong</cop><cop>New York, NY</cop><pub>Informa UK Ltd</pub><pmid>7680720</pmid><doi>10.3109/10799899309073669</doi><tpages>20</tpages></addata></record> |
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| identifier | ISSN: 1079-9893 |
| ispartof | Journal of receptor research, 1993, Vol.13 (1-4), p.393-412 |
| issn | 1079-9893 0197-5110 1532-4281 |
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| source | MEDLINE; Taylor & Francis; Taylor & Francis Medical Library - CRKN |
| subjects | Amino Acid Sequence Animals Biological and medical sciences Cell receptors Cell structures and functions Fundamental and applied biological sciences. Psychology In Vitro Techniques Ion Channels - drug effects Molecular and cellular biology Molecular Sequence Data Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine) Physostigmine - metabolism Physostigmine - pharmacology Receptors, Nicotinic - drug effects Receptors, Nicotinic - metabolism Torpedo |
| title | Biochemical Characterization of a Novel Channel-Activating Site on Nicotinic Acetylcholine Receptors |
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