Molecular evidence for a glycine-gated chloride channel in macrophages and leukocytes
Recent studies have demonstrated that glycine blunts the response of Kupffer cells to endotoxin. Based on pharmacological evidence, it was hypothesized that Kupffer cells and other macrophages contain a glycine-gated chloride channel similar to the glycine receptor expressed in neuronal tissues. Mor...
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Veröffentlicht in: | American journal of physiology: Gastrointestinal and liver physiology 2002-10, Vol.283 (4), p.G856-G863 |
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container_title | American journal of physiology: Gastrointestinal and liver physiology |
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creator | Froh, Matthias Thurman, Ronald G Wheeler, Michael D |
description | Recent studies have demonstrated that glycine blunts the response of Kupffer cells to endotoxin. Based on pharmacological evidence, it was hypothesized that Kupffer cells and other macrophages contain a glycine-gated chloride channel similar to the glycine receptor expressed in neuronal tissues. Moreover, glycine stimulates influx of radiolabeled chloride in Kupffer cells in a dose-dependent manner. RT-PCR was used to identify mRNA of both alpha- and beta-subunits of the glycine receptor in rat Kupffer cells, peritoneal neutrophils, and splenic and alveolar macrophages, similar to the sequence generated from rat spinal cord. Importantly, the sequence of the cloned Kupffer cell glycine receptor fragment for the beta-subunit was >95% homologous with the receptor from the spinal cord. Membranes of these cells also contain a protein that is immunoreactive with antibodies against the glycine-gated chloride channel. These data demonstrate that Kupffer cells, as well as other macrophages and leukocytes, express mRNA and protein for a glycine-gated chloride channel with both molecular and pharmacological properties similar to the channel expressed in the central nervous system. |
doi_str_mv | 10.1152/ajpgi.00503.2001 |
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Based on pharmacological evidence, it was hypothesized that Kupffer cells and other macrophages contain a glycine-gated chloride channel similar to the glycine receptor expressed in neuronal tissues. Moreover, glycine stimulates influx of radiolabeled chloride in Kupffer cells in a dose-dependent manner. RT-PCR was used to identify mRNA of both alpha- and beta-subunits of the glycine receptor in rat Kupffer cells, peritoneal neutrophils, and splenic and alveolar macrophages, similar to the sequence generated from rat spinal cord. Importantly, the sequence of the cloned Kupffer cell glycine receptor fragment for the beta-subunit was >95% homologous with the receptor from the spinal cord. Membranes of these cells also contain a protein that is immunoreactive with antibodies against the glycine-gated chloride channel. 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Based on pharmacological evidence, it was hypothesized that Kupffer cells and other macrophages contain a glycine-gated chloride channel similar to the glycine receptor expressed in neuronal tissues. Moreover, glycine stimulates influx of radiolabeled chloride in Kupffer cells in a dose-dependent manner. RT-PCR was used to identify mRNA of both alpha- and beta-subunits of the glycine receptor in rat Kupffer cells, peritoneal neutrophils, and splenic and alveolar macrophages, similar to the sequence generated from rat spinal cord. Importantly, the sequence of the cloned Kupffer cell glycine receptor fragment for the beta-subunit was >95% homologous with the receptor from the spinal cord. Membranes of these cells also contain a protein that is immunoreactive with antibodies against the glycine-gated chloride channel. These data demonstrate that Kupffer cells, as well as other macrophages and leukocytes, express mRNA and protein for a glycine-gated chloride channel with both molecular and pharmacological properties similar to the channel expressed in the central nervous system.</description><subject>Animals</subject><subject>Antibodies - immunology</subject><subject>Calcium - metabolism</subject><subject>Chloride Channels - analysis</subject><subject>Chloride Channels - immunology</subject><subject>Chloride Channels - physiology</subject><subject>Chlorides - metabolism</subject><subject>Glycine - pharmacology</subject><subject>Ion Channel Gating - drug effects</subject><subject>Isotope Labeling</subject><subject>Kupffer Cells - chemistry</subject><subject>Kupffer Cells - metabolism</subject><subject>Leukocytes - chemistry</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Macrophages - chemistry</subject><subject>Macrophages - metabolism</subject><subject>Macrophages, Alveolar - chemistry</subject><subject>Macrophages, Alveolar - metabolism</subject><subject>Male</subject><subject>Membrane Proteins - immunology</subject><subject>Neutrophils - chemistry</subject><subject>Neutrophils - metabolism</subject><subject>Peritoneum - cytology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Glycine - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Spleen - cytology</subject><issn>0193-1857</issn><issn>1522-1547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtPwzAQhC0EoqVw54R84pbiteM6PSLESyriQs-W42zSFCcOdoLUf0_6kDjtandmNPoIuQU2B5D8wWy7qp4zJpmYc8bgjEzHM09ApuqcTBksRQKZVBNyFeOWjUIOcEkmwDkXIpVTsv7wDu3gTKD4WxfYWqSlD9TQyu1s3WJSmR4LajfOh_E_LqZt0dG6pY2xwXcbU2Gkpi2ow-Hb212P8ZpclMZFvDnNGVm_PH89vSWrz9f3p8dVYsUC-iQrlCoXIBHQprjMszzNitLmKrPI8kUuUQEIkQkAsDkzsGQGZYEKOQeUKGbk_pjbBf8zYOx1U0eLzpkW_RC14kylgqWjkB2FY-MYA5a6C3Vjwk4D03uU-oBSH1DqPcrRcnfKHvIGi3_DiZ34A7V-cP8</recordid><startdate>20021001</startdate><enddate>20021001</enddate><creator>Froh, Matthias</creator><creator>Thurman, Ronald G</creator><creator>Wheeler, Michael D</creator><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>20021001</creationdate><title>Molecular evidence for a glycine-gated chloride channel in macrophages and leukocytes</title><author>Froh, Matthias ; Thurman, Ronald G ; Wheeler, Michael D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-8d77f615e1ec4e9b8b48dfcb78ce0b6b5e7113383111cb0a190ae5de7e221e5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Antibodies - immunology</topic><topic>Calcium - metabolism</topic><topic>Chloride Channels - analysis</topic><topic>Chloride Channels - immunology</topic><topic>Chloride Channels - physiology</topic><topic>Chlorides - metabolism</topic><topic>Glycine - pharmacology</topic><topic>Ion Channel Gating - drug effects</topic><topic>Isotope Labeling</topic><topic>Kupffer Cells - chemistry</topic><topic>Kupffer Cells - metabolism</topic><topic>Leukocytes - chemistry</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Macrophages - chemistry</topic><topic>Macrophages - metabolism</topic><topic>Macrophages, Alveolar - chemistry</topic><topic>Macrophages, Alveolar - metabolism</topic><topic>Male</topic><topic>Membrane Proteins - immunology</topic><topic>Neutrophils - chemistry</topic><topic>Neutrophils - metabolism</topic><topic>Peritoneum - cytology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Glycine - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Spleen - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Froh, Matthias</creatorcontrib><creatorcontrib>Thurman, Ronald G</creatorcontrib><creatorcontrib>Wheeler, Michael D</creatorcontrib><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>American journal of physiology: Gastrointestinal and liver physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Froh, Matthias</au><au>Thurman, Ronald G</au><au>Wheeler, Michael D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular evidence for a glycine-gated chloride channel in macrophages and leukocytes</atitle><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><date>2002-10-01</date><risdate>2002</risdate><volume>283</volume><issue>4</issue><spage>G856</spage><epage>G863</epage><pages>G856-G863</pages><issn>0193-1857</issn><eissn>1522-1547</eissn><abstract>Recent studies have demonstrated that glycine blunts the response of Kupffer cells to endotoxin. Based on pharmacological evidence, it was hypothesized that Kupffer cells and other macrophages contain a glycine-gated chloride channel similar to the glycine receptor expressed in neuronal tissues. Moreover, glycine stimulates influx of radiolabeled chloride in Kupffer cells in a dose-dependent manner. RT-PCR was used to identify mRNA of both alpha- and beta-subunits of the glycine receptor in rat Kupffer cells, peritoneal neutrophils, and splenic and alveolar macrophages, similar to the sequence generated from rat spinal cord. Importantly, the sequence of the cloned Kupffer cell glycine receptor fragment for the beta-subunit was >95% homologous with the receptor from the spinal cord. Membranes of these cells also contain a protein that is immunoreactive with antibodies against the glycine-gated chloride channel. These data demonstrate that Kupffer cells, as well as other macrophages and leukocytes, express mRNA and protein for a glycine-gated chloride channel with both molecular and pharmacological properties similar to the channel expressed in the central nervous system.</abstract><cop>United States</cop><pmid>12223345</pmid><doi>10.1152/ajpgi.00503.2001</doi></addata></record> |
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source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals |
subjects | Animals Antibodies - immunology Calcium - metabolism Chloride Channels - analysis Chloride Channels - immunology Chloride Channels - physiology Chlorides - metabolism Glycine - pharmacology Ion Channel Gating - drug effects Isotope Labeling Kupffer Cells - chemistry Kupffer Cells - metabolism Leukocytes - chemistry Lipopolysaccharides - pharmacology Macrophages - chemistry Macrophages - metabolism Macrophages, Alveolar - chemistry Macrophages, Alveolar - metabolism Male Membrane Proteins - immunology Neutrophils - chemistry Neutrophils - metabolism Peritoneum - cytology Rats Rats, Sprague-Dawley Receptors, Glycine - genetics Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Spleen - cytology |
title | Molecular evidence for a glycine-gated chloride channel in macrophages and leukocytes |
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