Loading…
New insights in endogenous modulation of ligand-gated ion channels: Histamine is an inverse agonist at strychnine sensitive glycine receptors
Histamine is involved in many physiological functions in the periphery and is an important neurotransmitter in the brain. It acts on metabotropic H1–H4 receptors mediating vasodilatation, bronchoconstriction and stimulation of gastric acid secretion. In the brain histamine is produced by neurons in...
Saved in:
| Published in: | European journal of pharmacology 2013-06, Vol.710 (1-3), p.59-66 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c386t-9abf836e7e0d29cbe8b97c6a4a0b62bf33bb58bec08745e92e482569af30c0073 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c386t-9abf836e7e0d29cbe8b97c6a4a0b62bf33bb58bec08745e92e482569af30c0073 |
| container_end_page | 66 |
| container_issue | 1-3 |
| container_start_page | 59 |
| container_title | European journal of pharmacology |
| container_volume | 710 |
| creator | Kletke, Olaf Sergeeva, Olga A. Lorenz, Philipp Oberland, Sonja Meier, Jochen C. Hatt, Hanns Gisselmann, Günter |
| description | Histamine is involved in many physiological functions in the periphery and is an important neurotransmitter in the brain. It acts on metabotropic H1–H4 receptors mediating vasodilatation, bronchoconstriction and stimulation of gastric acid secretion. In the brain histamine is produced by neurons in the tuberomamillary nucleus (TMN), which controls arousal. Histamine is also a positive modulator of the inhibitory Cys-loop ligand-gated ion channel GABAA. We investigated now its effect on the second member of inhibitory Cys-loop ligand-gated ion channels, the strychnine sensitive glycine receptor. We expressed different human and rat glycine receptor subunits in Xenopus laevis oocytes and characterized the effect of histamine using the two electrode voltage clamp technique. Furthermore we investigated native glycine receptors in hypothalamic neurons using the patch-clamp technique. Histamine inhibited α1β glycine receptors with an IC50 of 5.2±0.3mM. In presence of 10mM histamine the glycine dose–response curve was shifted, increasing the EC50 for glycine from 25.5±1.4μM to 42.4±2.3μM. In addition, histamine blocked the spontaneous activity of RNA-edited α3β glycine receptors. Histamine inhibited glycine receptors expressed in hypothalamic TMN neurons with an IC50 of 4.6±0.3mM. Our results give strong evidence that histamine is acting on the same binding site as glycine, being an inverse agonist that competitively antagonizes glycine receptors. Thus, we revealed histamine as an endogenous modulator of glycine receptors. |
| doi_str_mv | 10.1016/j.ejphar.2013.04.002 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1356369695</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014299913002896</els_id><sourcerecordid>1356369695</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-9abf836e7e0d29cbe8b97c6a4a0b62bf33bb58bec08745e92e482569af30c0073</originalsourceid><addsrcrecordid>eNp9kUGO1DAQRSMEYpqBGyDwkk1C2U6cmAUSGgGDNIIFzNpynErarcRubHejPgR3xlEGlqxslV_9Kv9fFC8pVBSoeHuo8HDc61AxoLyCugJgj4od7VpZQkvZ42IHQOuSSSmvimcxHgCgkax5WlwxLoA3jO2K31_xF7Eu2mmfYr4QdIOf0PlTJIsfTrNO1jviRzLbSbuhnHTCgaw1s9fO4RzfkVsbk16sQ2Ij0S7LnDFEJHryLj8RnUhM4WL2bmUi5nHJnpFM88WslYAGj8mH-Lx4Muo54ouH87q4__Txx81tefft85ebD3el4Z1IpdT92HGBLcLApOmx62VrhK419IL1I-d933Q9GujaukHJsO5YI6QeORiAll8XbzbdY_A_TxiTWmw0OM_aYf65orwRXEghm4zWG2qCjzHgqI7BLjpcFAW1BqEOagtCrUEoqFUOIre9ephw6hcc_jX9dT4Drzdg1F7pKdio7r9nhSanVNNa0Ey834jsMZ4tBhWNRWdwsNmwpAZv_7_DHzM9qAw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1356369695</pqid></control><display><type>article</type><title>New insights in endogenous modulation of ligand-gated ion channels: Histamine is an inverse agonist at strychnine sensitive glycine receptors</title><source>ScienceDirect Freedom Collection</source><creator>Kletke, Olaf ; Sergeeva, Olga A. ; Lorenz, Philipp ; Oberland, Sonja ; Meier, Jochen C. ; Hatt, Hanns ; Gisselmann, Günter</creator><creatorcontrib>Kletke, Olaf ; Sergeeva, Olga A. ; Lorenz, Philipp ; Oberland, Sonja ; Meier, Jochen C. ; Hatt, Hanns ; Gisselmann, Günter</creatorcontrib><description>Histamine is involved in many physiological functions in the periphery and is an important neurotransmitter in the brain. It acts on metabotropic H1–H4 receptors mediating vasodilatation, bronchoconstriction and stimulation of gastric acid secretion. In the brain histamine is produced by neurons in the tuberomamillary nucleus (TMN), which controls arousal. Histamine is also a positive modulator of the inhibitory Cys-loop ligand-gated ion channel GABAA. We investigated now its effect on the second member of inhibitory Cys-loop ligand-gated ion channels, the strychnine sensitive glycine receptor. We expressed different human and rat glycine receptor subunits in Xenopus laevis oocytes and characterized the effect of histamine using the two electrode voltage clamp technique. Furthermore we investigated native glycine receptors in hypothalamic neurons using the patch-clamp technique. Histamine inhibited α1β glycine receptors with an IC50 of 5.2±0.3mM. In presence of 10mM histamine the glycine dose–response curve was shifted, increasing the EC50 for glycine from 25.5±1.4μM to 42.4±2.3μM. In addition, histamine blocked the spontaneous activity of RNA-edited α3β glycine receptors. Histamine inhibited glycine receptors expressed in hypothalamic TMN neurons with an IC50 of 4.6±0.3mM. Our results give strong evidence that histamine is acting on the same binding site as glycine, being an inverse agonist that competitively antagonizes glycine receptors. Thus, we revealed histamine as an endogenous modulator of glycine receptors.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2013.04.002</identifier><identifier>PMID: 23603522</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>agonists ; Animals ; binding sites ; brain ; bronchoconstriction ; Competitive antagonist ; DNA, Complementary - genetics ; dose response ; electrodes ; Endogenous modulator ; gastric acid ; Glycine ; Histamine ; Histamine - pharmacology ; Humans ; Hypothalamus - cytology ; inhibitory concentration 50 ; ion channels ; Ligand-gated ion channel ; Male ; Mice, Inbred C57BL ; Modulation ; neurons ; Neurons - drug effects ; Neurons - metabolism ; oocytes ; Oocytes - drug effects ; Oocytes - metabolism ; patch-clamp technique ; pharmacology ; Protein Subunits - antagonists & inhibitors ; Protein Subunits - genetics ; Protein Subunits - metabolism ; Rats ; receptors ; Receptors, Glycine - antagonists & inhibitors ; Receptors, Glycine - genetics ; Receptors, Glycine - metabolism ; Recombinant Proteins - metabolism ; secretion ; strychnine ; vasodilation ; Xenopus laevis ; Xenopus laevis - genetics</subject><ispartof>European journal of pharmacology, 2013-06, Vol.710 (1-3), p.59-66</ispartof><rights>2013 Elsevier B.V.</rights><rights>Copyright © 2013 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-9abf836e7e0d29cbe8b97c6a4a0b62bf33bb58bec08745e92e482569af30c0073</citedby><cites>FETCH-LOGICAL-c386t-9abf836e7e0d29cbe8b97c6a4a0b62bf33bb58bec08745e92e482569af30c0073</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23603522$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kletke, Olaf</creatorcontrib><creatorcontrib>Sergeeva, Olga A.</creatorcontrib><creatorcontrib>Lorenz, Philipp</creatorcontrib><creatorcontrib>Oberland, Sonja</creatorcontrib><creatorcontrib>Meier, Jochen C.</creatorcontrib><creatorcontrib>Hatt, Hanns</creatorcontrib><creatorcontrib>Gisselmann, Günter</creatorcontrib><title>New insights in endogenous modulation of ligand-gated ion channels: Histamine is an inverse agonist at strychnine sensitive glycine receptors</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Histamine is involved in many physiological functions in the periphery and is an important neurotransmitter in the brain. It acts on metabotropic H1–H4 receptors mediating vasodilatation, bronchoconstriction and stimulation of gastric acid secretion. In the brain histamine is produced by neurons in the tuberomamillary nucleus (TMN), which controls arousal. Histamine is also a positive modulator of the inhibitory Cys-loop ligand-gated ion channel GABAA. We investigated now its effect on the second member of inhibitory Cys-loop ligand-gated ion channels, the strychnine sensitive glycine receptor. We expressed different human and rat glycine receptor subunits in Xenopus laevis oocytes and characterized the effect of histamine using the two electrode voltage clamp technique. Furthermore we investigated native glycine receptors in hypothalamic neurons using the patch-clamp technique. Histamine inhibited α1β glycine receptors with an IC50 of 5.2±0.3mM. In presence of 10mM histamine the glycine dose–response curve was shifted, increasing the EC50 for glycine from 25.5±1.4μM to 42.4±2.3μM. In addition, histamine blocked the spontaneous activity of RNA-edited α3β glycine receptors. Histamine inhibited glycine receptors expressed in hypothalamic TMN neurons with an IC50 of 4.6±0.3mM. Our results give strong evidence that histamine is acting on the same binding site as glycine, being an inverse agonist that competitively antagonizes glycine receptors. Thus, we revealed histamine as an endogenous modulator of glycine receptors.</description><subject>agonists</subject><subject>Animals</subject><subject>binding sites</subject><subject>brain</subject><subject>bronchoconstriction</subject><subject>Competitive antagonist</subject><subject>DNA, Complementary - genetics</subject><subject>dose response</subject><subject>electrodes</subject><subject>Endogenous modulator</subject><subject>gastric acid</subject><subject>Glycine</subject><subject>Histamine</subject><subject>Histamine - pharmacology</subject><subject>Humans</subject><subject>Hypothalamus - cytology</subject><subject>inhibitory concentration 50</subject><subject>ion channels</subject><subject>Ligand-gated ion channel</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Modulation</subject><subject>neurons</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>oocytes</subject><subject>Oocytes - drug effects</subject><subject>Oocytes - metabolism</subject><subject>patch-clamp technique</subject><subject>pharmacology</subject><subject>Protein Subunits - antagonists & inhibitors</subject><subject>Protein Subunits - genetics</subject><subject>Protein Subunits - metabolism</subject><subject>Rats</subject><subject>receptors</subject><subject>Receptors, Glycine - antagonists & inhibitors</subject><subject>Receptors, Glycine - genetics</subject><subject>Receptors, Glycine - metabolism</subject><subject>Recombinant Proteins - metabolism</subject><subject>secretion</subject><subject>strychnine</subject><subject>vasodilation</subject><subject>Xenopus laevis</subject><subject>Xenopus laevis - genetics</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kUGO1DAQRSMEYpqBGyDwkk1C2U6cmAUSGgGDNIIFzNpynErarcRubHejPgR3xlEGlqxslV_9Kv9fFC8pVBSoeHuo8HDc61AxoLyCugJgj4od7VpZQkvZ42IHQOuSSSmvimcxHgCgkax5WlwxLoA3jO2K31_xF7Eu2mmfYr4QdIOf0PlTJIsfTrNO1jviRzLbSbuhnHTCgaw1s9fO4RzfkVsbk16sQ2Ij0S7LnDFEJHryLj8RnUhM4WL2bmUi5nHJnpFM88WslYAGj8mH-Lx4Muo54ouH87q4__Txx81tefft85ebD3el4Z1IpdT92HGBLcLApOmx62VrhK419IL1I-d933Q9GujaukHJsO5YI6QeORiAll8XbzbdY_A_TxiTWmw0OM_aYf65orwRXEghm4zWG2qCjzHgqI7BLjpcFAW1BqEOagtCrUEoqFUOIre9ephw6hcc_jX9dT4Drzdg1F7pKdio7r9nhSanVNNa0Ey834jsMZ4tBhWNRWdwsNmwpAZv_7_DHzM9qAw</recordid><startdate>20130615</startdate><enddate>20130615</enddate><creator>Kletke, Olaf</creator><creator>Sergeeva, Olga A.</creator><creator>Lorenz, Philipp</creator><creator>Oberland, Sonja</creator><creator>Meier, Jochen C.</creator><creator>Hatt, Hanns</creator><creator>Gisselmann, Günter</creator><general>Elsevier B.V</general><scope>FBQ</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>20130615</creationdate><title>New insights in endogenous modulation of ligand-gated ion channels: Histamine is an inverse agonist at strychnine sensitive glycine receptors</title><author>Kletke, Olaf ; Sergeeva, Olga A. ; Lorenz, Philipp ; Oberland, Sonja ; Meier, Jochen C. ; Hatt, Hanns ; Gisselmann, Günter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-9abf836e7e0d29cbe8b97c6a4a0b62bf33bb58bec08745e92e482569af30c0073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>agonists</topic><topic>Animals</topic><topic>binding sites</topic><topic>brain</topic><topic>bronchoconstriction</topic><topic>Competitive antagonist</topic><topic>DNA, Complementary - genetics</topic><topic>dose response</topic><topic>electrodes</topic><topic>Endogenous modulator</topic><topic>gastric acid</topic><topic>Glycine</topic><topic>Histamine</topic><topic>Histamine - pharmacology</topic><topic>Humans</topic><topic>Hypothalamus - cytology</topic><topic>inhibitory concentration 50</topic><topic>ion channels</topic><topic>Ligand-gated ion channel</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Modulation</topic><topic>neurons</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>oocytes</topic><topic>Oocytes - drug effects</topic><topic>Oocytes - metabolism</topic><topic>patch-clamp technique</topic><topic>pharmacology</topic><topic>Protein Subunits - antagonists & inhibitors</topic><topic>Protein Subunits - genetics</topic><topic>Protein Subunits - metabolism</topic><topic>Rats</topic><topic>receptors</topic><topic>Receptors, Glycine - antagonists & inhibitors</topic><topic>Receptors, Glycine - genetics</topic><topic>Receptors, Glycine - metabolism</topic><topic>Recombinant Proteins - metabolism</topic><topic>secretion</topic><topic>strychnine</topic><topic>vasodilation</topic><topic>Xenopus laevis</topic><topic>Xenopus laevis - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kletke, Olaf</creatorcontrib><creatorcontrib>Sergeeva, Olga A.</creatorcontrib><creatorcontrib>Lorenz, Philipp</creatorcontrib><creatorcontrib>Oberland, Sonja</creatorcontrib><creatorcontrib>Meier, Jochen C.</creatorcontrib><creatorcontrib>Hatt, Hanns</creatorcontrib><creatorcontrib>Gisselmann, Günter</creatorcontrib><collection>AGRIS</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>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kletke, Olaf</au><au>Sergeeva, Olga A.</au><au>Lorenz, Philipp</au><au>Oberland, Sonja</au><au>Meier, Jochen C.</au><au>Hatt, Hanns</au><au>Gisselmann, Günter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New insights in endogenous modulation of ligand-gated ion channels: Histamine is an inverse agonist at strychnine sensitive glycine receptors</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2013-06-15</date><risdate>2013</risdate><volume>710</volume><issue>1-3</issue><spage>59</spage><epage>66</epage><pages>59-66</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><notes>http://dx.doi.org/10.1016/j.ejphar.2013.04.002</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Histamine is involved in many physiological functions in the periphery and is an important neurotransmitter in the brain. It acts on metabotropic H1–H4 receptors mediating vasodilatation, bronchoconstriction and stimulation of gastric acid secretion. In the brain histamine is produced by neurons in the tuberomamillary nucleus (TMN), which controls arousal. Histamine is also a positive modulator of the inhibitory Cys-loop ligand-gated ion channel GABAA. We investigated now its effect on the second member of inhibitory Cys-loop ligand-gated ion channels, the strychnine sensitive glycine receptor. We expressed different human and rat glycine receptor subunits in Xenopus laevis oocytes and characterized the effect of histamine using the two electrode voltage clamp technique. Furthermore we investigated native glycine receptors in hypothalamic neurons using the patch-clamp technique. Histamine inhibited α1β glycine receptors with an IC50 of 5.2±0.3mM. In presence of 10mM histamine the glycine dose–response curve was shifted, increasing the EC50 for glycine from 25.5±1.4μM to 42.4±2.3μM. In addition, histamine blocked the spontaneous activity of RNA-edited α3β glycine receptors. Histamine inhibited glycine receptors expressed in hypothalamic TMN neurons with an IC50 of 4.6±0.3mM. Our results give strong evidence that histamine is acting on the same binding site as glycine, being an inverse agonist that competitively antagonizes glycine receptors. Thus, we revealed histamine as an endogenous modulator of glycine receptors.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>23603522</pmid><doi>10.1016/j.ejphar.2013.04.002</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-2999 |
| ispartof | European journal of pharmacology, 2013-06, Vol.710 (1-3), p.59-66 |
| issn | 0014-2999 1879-0712 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1356369695 |
| source | ScienceDirect Freedom Collection |
| subjects | agonists Animals binding sites brain bronchoconstriction Competitive antagonist DNA, Complementary - genetics dose response electrodes Endogenous modulator gastric acid Glycine Histamine Histamine - pharmacology Humans Hypothalamus - cytology inhibitory concentration 50 ion channels Ligand-gated ion channel Male Mice, Inbred C57BL Modulation neurons Neurons - drug effects Neurons - metabolism oocytes Oocytes - drug effects Oocytes - metabolism patch-clamp technique pharmacology Protein Subunits - antagonists & inhibitors Protein Subunits - genetics Protein Subunits - metabolism Rats receptors Receptors, Glycine - antagonists & inhibitors Receptors, Glycine - genetics Receptors, Glycine - metabolism Recombinant Proteins - metabolism secretion strychnine vasodilation Xenopus laevis Xenopus laevis - genetics |
| title | New insights in endogenous modulation of ligand-gated ion channels: Histamine is an inverse agonist at strychnine sensitive glycine receptors |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-23T07%3A22%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=New%20insights%20in%20endogenous%20modulation%20of%20ligand-gated%20ion%20channels:%20Histamine%20is%20an%20inverse%20agonist%20at%20strychnine%20sensitive%20glycine%20receptors&rft.jtitle=European%20journal%20of%20pharmacology&rft.au=Kletke,%20Olaf&rft.date=2013-06-15&rft.volume=710&rft.issue=1-3&rft.spage=59&rft.epage=66&rft.pages=59-66&rft.issn=0014-2999&rft.eissn=1879-0712&rft_id=info:doi/10.1016/j.ejphar.2013.04.002&rft_dat=%3Cproquest_cross%3E1356369695%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c386t-9abf836e7e0d29cbe8b97c6a4a0b62bf33bb58bec08745e92e482569af30c0073%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1356369695&rft_id=info:pmid/23603522&rfr_iscdi=true |