Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic β cells
In an unanticipated cross-talk between the steroid and insulin endocrine systems, the neuroactive steroid pregnenolone sulphate is found to activate the TRPM3 channel, leading to enhanced insulin secretion from pancreatic islets. Transient receptor potential (TRP) cation channels are renowned for th...
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| Veröffentlicht in: | Nature cell biology 2008-12, Vol.10 (12), p.1421-1430 |
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| creator | Wagner, Thomas F.J. Loch, Sabine Lambert, Sachar Straub, Isabelle Mannebach, Stefanie Mathar, Ilka Düfer, Martina Lis, Annette Flockerzi, Veit Philipp, Stephan E. Oberwinkler, Johannes |
| description | In an unanticipated cross-talk between the steroid and insulin endocrine systems, the neuroactive steroid pregnenolone sulphate is found to activate the TRPM3 channel, leading to enhanced insulin secretion from pancreatic islets.
Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing β cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems. |
| doi_str_mv | 10.1038/ncb1801 |
| format | Article |
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Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing β cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb1801</identifier><identifier>PMID: 18978782</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Biomedical and Life Sciences ; Biophysical Phenomena - drug effects ; Calcium Signaling - drug effects ; Cancer Research ; Cations, Monovalent - pharmacology ; Cell Biology ; Cell Line ; Developmental Biology ; Down-Regulation - drug effects ; Extracellular Space - drug effects ; Extracellular Space - metabolism ; Genetic aspects ; Health aspects ; Humans ; Insulin - metabolism ; Insulin Secretion ; Insulin-Secreting Cells - drug effects ; Insulin-Secreting Cells - metabolism ; Ion Channel Gating - drug effects ; Ion channels ; Life Sciences ; Mice ; Nifedipine - pharmacology ; Pancreatic beta cells ; Permeability - drug effects ; Physiological aspects ; Pregnenolone - pharmacology ; Rats ; Receptors ; Receptors, Steroid - metabolism ; RNA, Small Interfering - metabolism ; Stem Cells ; Steroid hormones ; TRPM Cation Channels - metabolism</subject><ispartof>Nature cell biology, 2008-12, Vol.10 (12), p.1421-1430</ispartof><rights>Springer Nature Limited 2008</rights><rights>COPYRIGHT 2008 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-b2965eb930b201ebc18c9985c8278dd0267faad19b09e2fa68fedef12ed00c223</citedby><cites>FETCH-LOGICAL-c451t-b2965eb930b201ebc18c9985c8278dd0267faad19b09e2fa68fedef12ed00c223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ncb1801$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ncb1801$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18978782$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wagner, Thomas F.J.</creatorcontrib><creatorcontrib>Loch, Sabine</creatorcontrib><creatorcontrib>Lambert, Sachar</creatorcontrib><creatorcontrib>Straub, Isabelle</creatorcontrib><creatorcontrib>Mannebach, Stefanie</creatorcontrib><creatorcontrib>Mathar, Ilka</creatorcontrib><creatorcontrib>Düfer, Martina</creatorcontrib><creatorcontrib>Lis, Annette</creatorcontrib><creatorcontrib>Flockerzi, Veit</creatorcontrib><creatorcontrib>Philipp, Stephan E.</creatorcontrib><creatorcontrib>Oberwinkler, Johannes</creatorcontrib><title>Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic β cells</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>In an unanticipated cross-talk between the steroid and insulin endocrine systems, the neuroactive steroid pregnenolone sulphate is found to activate the TRPM3 channel, leading to enhanced insulin secretion from pancreatic islets.
Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing β cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biophysical Phenomena - drug effects</subject><subject>Calcium Signaling - drug effects</subject><subject>Cancer Research</subject><subject>Cations, Monovalent - pharmacology</subject><subject>Cell Biology</subject><subject>Cell Line</subject><subject>Developmental Biology</subject><subject>Down-Regulation - drug effects</subject><subject>Extracellular Space - drug effects</subject><subject>Extracellular Space - metabolism</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Ion Channel Gating - drug effects</subject><subject>Ion channels</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Nifedipine - pharmacology</subject><subject>Pancreatic beta cells</subject><subject>Permeability - drug effects</subject><subject>Physiological aspects</subject><subject>Pregnenolone - pharmacology</subject><subject>Rats</subject><subject>Receptors</subject><subject>Receptors, Steroid - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Stem Cells</subject><subject>Steroid hormones</subject><subject>TRPM Cation Channels - metabolism</subject><issn>1465-7392</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0dlKxDAUANAgijv-gQQEl4dqknba5FHEDRTB5Tmm6e0Y6SQ1SUF_yw_xm8wwgzIoech27iU3F6EdSo4pyfmJ1TXlhC6hdVpUZVaUlVierstRVuWCraGNEF4JoUVBqlW0RrmoeMXZOnp-9MoGAzZiDxr66DzuXUx7ozp8m2P9oqyFLmDlARtnXfSuNxqHCN6Z5icqYGNxr6z2oGK6__rEGroubKGVVnUBtufzJnq6OH88u8pu7i6vz05vMl2MaMxqJsoR1CInNSMUak25FoKPNGcVbxrCyqpVqqGiJgJYq0reQgMtZdAQohnLN9H-LG_v3dsAIcqJCdMXKAtuCLIUvBCsFAnuzeBYdSCNbVNFSk-xPKWC5DnLC57U8T8qjQYmRjsLrUnnCwFHCwHJRHiPYzWEIK8f7hftwcxq70Lw0Mrem4nyH5ISOe2nnPczyd15VUM9gebXzRuYwOEMhHRlx-Dlqxu8TT_9J9c3nMeoPg</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Wagner, Thomas F.J.</creator><creator>Loch, Sabine</creator><creator>Lambert, Sachar</creator><creator>Straub, Isabelle</creator><creator>Mannebach, Stefanie</creator><creator>Mathar, Ilka</creator><creator>Düfer, Martina</creator><creator>Lis, Annette</creator><creator>Flockerzi, Veit</creator><creator>Philipp, Stephan E.</creator><creator>Oberwinkler, Johannes</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>ISR</scope><scope>7X8</scope></search><sort><creationdate>20081201</creationdate><title>Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic β cells</title><author>Wagner, Thomas F.J. ; Loch, Sabine ; Lambert, Sachar ; Straub, Isabelle ; Mannebach, Stefanie ; Mathar, Ilka ; Düfer, Martina ; Lis, Annette ; Flockerzi, Veit ; Philipp, Stephan E. ; Oberwinkler, Johannes</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-b2965eb930b201ebc18c9985c8278dd0267faad19b09e2fa68fedef12ed00c223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biophysical Phenomena - drug effects</topic><topic>Calcium Signaling - drug effects</topic><topic>Cancer Research</topic><topic>Cations, Monovalent - pharmacology</topic><topic>Cell Biology</topic><topic>Cell Line</topic><topic>Developmental Biology</topic><topic>Down-Regulation - drug effects</topic><topic>Extracellular Space - drug effects</topic><topic>Extracellular Space - metabolism</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>Insulin-Secreting Cells - drug effects</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Ion Channel Gating - drug effects</topic><topic>Ion channels</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Nifedipine - pharmacology</topic><topic>Pancreatic beta cells</topic><topic>Permeability - drug effects</topic><topic>Physiological aspects</topic><topic>Pregnenolone - pharmacology</topic><topic>Rats</topic><topic>Receptors</topic><topic>Receptors, Steroid - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Stem Cells</topic><topic>Steroid hormones</topic><topic>TRPM Cation Channels - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wagner, Thomas F.J.</creatorcontrib><creatorcontrib>Loch, Sabine</creatorcontrib><creatorcontrib>Lambert, Sachar</creatorcontrib><creatorcontrib>Straub, Isabelle</creatorcontrib><creatorcontrib>Mannebach, Stefanie</creatorcontrib><creatorcontrib>Mathar, Ilka</creatorcontrib><creatorcontrib>Düfer, Martina</creatorcontrib><creatorcontrib>Lis, Annette</creatorcontrib><creatorcontrib>Flockerzi, Veit</creatorcontrib><creatorcontrib>Philipp, Stephan E.</creatorcontrib><creatorcontrib>Oberwinkler, Johannes</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wagner, Thomas F.J.</au><au>Loch, Sabine</au><au>Lambert, Sachar</au><au>Straub, Isabelle</au><au>Mannebach, Stefanie</au><au>Mathar, Ilka</au><au>Düfer, Martina</au><au>Lis, Annette</au><au>Flockerzi, Veit</au><au>Philipp, Stephan E.</au><au>Oberwinkler, Johannes</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic β cells</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>10</volume><issue>12</issue><spage>1421</spage><epage>1430</epage><pages>1421-1430</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>In an unanticipated cross-talk between the steroid and insulin endocrine systems, the neuroactive steroid pregnenolone sulphate is found to activate the TRPM3 channel, leading to enhanced insulin secretion from pancreatic islets.
Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing β cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>18978782</pmid><doi>10.1038/ncb1801</doi><tpages>10</tpages></addata></record> |
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| ispartof | Nature cell biology, 2008-12, Vol.10 (12), p.1421-1430 |
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| subjects | Animals Biomedical and Life Sciences Biophysical Phenomena - drug effects Calcium Signaling - drug effects Cancer Research Cations, Monovalent - pharmacology Cell Biology Cell Line Developmental Biology Down-Regulation - drug effects Extracellular Space - drug effects Extracellular Space - metabolism Genetic aspects Health aspects Humans Insulin - metabolism Insulin Secretion Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Ion Channel Gating - drug effects Ion channels Life Sciences Mice Nifedipine - pharmacology Pancreatic beta cells Permeability - drug effects Physiological aspects Pregnenolone - pharmacology Rats Receptors Receptors, Steroid - metabolism RNA, Small Interfering - metabolism Stem Cells Steroid hormones TRPM Cation Channels - metabolism |
| title | Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic β cells |
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