Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia
Activating calcium sensing receptor (CaSR) mutations cause autosomal dominant hypocalcemia (ADH) characterized by low serum calcium, inappropriately low PTH and relative hypercalciuria. Four activating CaSR mutations cause additional renal wasting of sodium, chloride and other salts, a condition cal...
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| creator | Letz, Saskia Haag, Christine Schulze, Egbert Frank-Raue, Karin Raue, Friedhelm Hofner, Benjamin Mayr, Bernhard Schöfl, Christof |
| description | Activating calcium sensing receptor (CaSR) mutations cause autosomal dominant hypocalcemia (ADH) characterized by low serum calcium, inappropriately low PTH and relative hypercalciuria. Four activating CaSR mutations cause additional renal wasting of sodium, chloride and other salts, a condition called Bartter syndrome (BS) type 5. Until today there is no specific medical treatment for BS type 5 and ADH. We investigated the effects of different allosteric CaSR antagonists (calcilytics) on activating CaSR mutants.
All 4 known mutations causing BS type 5 and five ADH mutations were expressed in HEK 293T cells and receptor signalling was studied by measurement of intracellular free calcium in response to extracellular calcium ([Ca2+]o). To investigate the effect of calcilytics, cells were stimulated with 3 mM [Ca2+]o in the presence or absence of NPS-2143, ATF936 or AXT914.
All BS type 5 and ADH mutants showed enhanced signalling activity to [Ca2+]o with left shifted dose response curves. In contrast to the amino alcohol NPS-2143, which was only partially effective, the quinazolinone calcilytics ATF936 and AXT914 significantly mitigated excessive cytosolic calcium signalling of all BS type 5 and ADH mutants studied. When these mutants were co-expressed with wild-type CaSR to approximate heterozygosity in patients, ATF936 and AXT914 were also effective on all mutants.
The calcilytics ATF936 and AXT914 are capable of attenuating enhanced cytosolic calcium signalling activity of CaSR mutations causing BS type 5 and ADH. Quinazolinone calcilytics might therefore offer a novel treatment option for patients with activating CaSR mutations. |
| doi_str_mv | 10.1371/journal.pone.0115178 |
| format | Article |
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All 4 known mutations causing BS type 5 and five ADH mutations were expressed in HEK 293T cells and receptor signalling was studied by measurement of intracellular free calcium in response to extracellular calcium ([Ca2+]o). To investigate the effect of calcilytics, cells were stimulated with 3 mM [Ca2+]o in the presence or absence of NPS-2143, ATF936 or AXT914.
All BS type 5 and ADH mutants showed enhanced signalling activity to [Ca2+]o with left shifted dose response curves. In contrast to the amino alcohol NPS-2143, which was only partially effective, the quinazolinone calcilytics ATF936 and AXT914 significantly mitigated excessive cytosolic calcium signalling of all BS type 5 and ADH mutants studied. When these mutants were co-expressed with wild-type CaSR to approximate heterozygosity in patients, ATF936 and AXT914 were also effective on all mutants.
The calcilytics ATF936 and AXT914 are capable of attenuating enhanced cytosolic calcium signalling activity of CaSR mutations causing BS type 5 and ADH. Quinazolinone calcilytics might therefore offer a novel treatment option for patients with activating CaSR mutations.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0115178</identifier><identifier>PMID: 25506941</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alcohol ; Alcohols ; Allosteric properties ; Antagonists ; Bartter Syndrome - genetics ; Biology and Life Sciences ; Calcium ; Calcium (blood) ; Calcium (extracellular) ; Calcium (intracellular) ; Calcium - metabolism ; Calcium ions ; Calcium Signaling - drug effects ; Calcium Signaling - genetics ; Calcium signalling ; Calcium-sensing receptors ; Confidence intervals ; Diabetes ; Drug dosages ; Endocrinology ; HEK293 Cells ; Heterozygosity ; Humans ; Hypercalciuria ; Hypercalciuria - genetics ; Hypocalcemia ; Hypocalcemia - genetics ; Hypoparathyroidism - congenital ; Hypoparathyroidism - genetics ; Intracellular signalling ; Medical treatment ; Medicine and Health Sciences ; Mutants ; Mutation ; Naphthalenes - pharmacology ; Parathyroid hormone ; Patients ; Quinazolinone ; Quinazolinones - pharmacology ; Receptors, Calcium-Sensing - drug effects ; Receptors, Calcium-Sensing - genetics ; Salts ; Signal transduction ; Sodium ; Vitamin deficiency</subject><ispartof>PloS one, 2014-12, Vol.9 (12), p.e115178-e115178</ispartof><rights>2014 Letz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Letz et al 2014 Letz et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-71386a5ebd8c6448aa39168e957b7dde607019df74238c04a81f9b0dc51f3cd43</citedby><cites>FETCH-LOGICAL-c526t-71386a5ebd8c6448aa39168e957b7dde607019df74238c04a81f9b0dc51f3cd43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266668/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266668/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79472,79473</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25506941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Valenti, Giovanna</contributor><creatorcontrib>Letz, Saskia</creatorcontrib><creatorcontrib>Haag, Christine</creatorcontrib><creatorcontrib>Schulze, Egbert</creatorcontrib><creatorcontrib>Frank-Raue, Karin</creatorcontrib><creatorcontrib>Raue, Friedhelm</creatorcontrib><creatorcontrib>Hofner, Benjamin</creatorcontrib><creatorcontrib>Mayr, Bernhard</creatorcontrib><creatorcontrib>Schöfl, Christof</creatorcontrib><title>Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Activating calcium sensing receptor (CaSR) mutations cause autosomal dominant hypocalcemia (ADH) characterized by low serum calcium, inappropriately low PTH and relative hypercalciuria. Four activating CaSR mutations cause additional renal wasting of sodium, chloride and other salts, a condition called Bartter syndrome (BS) type 5. Until today there is no specific medical treatment for BS type 5 and ADH. We investigated the effects of different allosteric CaSR antagonists (calcilytics) on activating CaSR mutants.
All 4 known mutations causing BS type 5 and five ADH mutations were expressed in HEK 293T cells and receptor signalling was studied by measurement of intracellular free calcium in response to extracellular calcium ([Ca2+]o). To investigate the effect of calcilytics, cells were stimulated with 3 mM [Ca2+]o in the presence or absence of NPS-2143, ATF936 or AXT914.
All BS type 5 and ADH mutants showed enhanced signalling activity to [Ca2+]o with left shifted dose response curves. In contrast to the amino alcohol NPS-2143, which was only partially effective, the quinazolinone calcilytics ATF936 and AXT914 significantly mitigated excessive cytosolic calcium signalling of all BS type 5 and ADH mutants studied. When these mutants were co-expressed with wild-type CaSR to approximate heterozygosity in patients, ATF936 and AXT914 were also effective on all mutants.
The calcilytics ATF936 and AXT914 are capable of attenuating enhanced cytosolic calcium signalling activity of CaSR mutations causing BS type 5 and ADH. Quinazolinone calcilytics might therefore offer a novel treatment option for patients with activating CaSR mutations.</description><subject>Alcohol</subject><subject>Alcohols</subject><subject>Allosteric properties</subject><subject>Antagonists</subject><subject>Bartter Syndrome - genetics</subject><subject>Biology and Life Sciences</subject><subject>Calcium</subject><subject>Calcium (blood)</subject><subject>Calcium (extracellular)</subject><subject>Calcium (intracellular)</subject><subject>Calcium - metabolism</subject><subject>Calcium ions</subject><subject>Calcium Signaling - drug effects</subject><subject>Calcium Signaling - genetics</subject><subject>Calcium signalling</subject><subject>Calcium-sensing receptors</subject><subject>Confidence intervals</subject><subject>Diabetes</subject><subject>Drug dosages</subject><subject>Endocrinology</subject><subject>HEK293 Cells</subject><subject>Heterozygosity</subject><subject>Humans</subject><subject>Hypercalciuria</subject><subject>Hypercalciuria - genetics</subject><subject>Hypocalcemia</subject><subject>Hypocalcemia - genetics</subject><subject>Hypoparathyroidism - congenital</subject><subject>Hypoparathyroidism - genetics</subject><subject>Intracellular signalling</subject><subject>Medical treatment</subject><subject>Medicine and Health Sciences</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Naphthalenes - pharmacology</subject><subject>Parathyroid hormone</subject><subject>Patients</subject><subject>Quinazolinone</subject><subject>Quinazolinones - pharmacology</subject><subject>Receptors, Calcium-Sensing - drug effects</subject><subject>Receptors, Calcium-Sensing - genetics</subject><subject>Salts</subject><subject>Signal transduction</subject><subject>Sodium</subject><subject>Vitamin deficiency</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptks1u1DAQxyMEoqXwBggscWkPWezYcZxLpaWiUKkCJBaJm-W1J7teOfHWTirCE_MYeLPbqkX4YmvmN__58GTZa4JnhFbk_cYPoVNutvUdzDAhJanEk-yY1LTIeYHp0wfvo-xFjBuMSyo4f54dFWWJec3IcfZn3trOI-W0X3uXo9Mv377nBWH0DKnOoJvBduq3d4npIDcQ7C0YpBNu3dhbHdHpfHFZUz7R85-LmrAzZGzTQICut8q5EbW2tyvVA4JfGmJMEijaVao9ya6Qb_Z6Q5tH6OLOFEDDtvcBtUOvuj4mYJgcH1Toewgojp0JvgW0GLeAyim5GnoffascMj71lOLQetz6nTa0Vr3MnjXKRXh1uE-yH5cfFxef8-uvn64u5te5Lgve5xVJI1IlLI3QnDGhFK0JF1CX1bIyBjiuMKlNU7GCCo2ZEqSpl9jokjRUG0ZPsrd73a3zUR4-KUrCKa9KSguRiKs9YbzayG2wrQqj9MrKyeDDSqY2rXYggRhc8ZSE1ZSphgtRVqIoC9AClmTKdn7INixbMDrNPCj3SPSxp7NrufK3khU8nV0xpweB4G8GiL1sbdTgnOrAD1PdNROcUpzQd_-g_--O7SkdfIwBmvtiCJa7xb2LkrvFlYfFTWFvHjZyH3S3qfQvUizvog</recordid><startdate>20141215</startdate><enddate>20141215</enddate><creator>Letz, Saskia</creator><creator>Haag, Christine</creator><creator>Schulze, Egbert</creator><creator>Frank-Raue, Karin</creator><creator>Raue, Friedhelm</creator><creator>Hofner, Benjamin</creator><creator>Mayr, Bernhard</creator><creator>Schöfl, Christof</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141215</creationdate><title>Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia</title><author>Letz, Saskia ; Haag, Christine ; Schulze, Egbert ; Frank-Raue, Karin ; Raue, Friedhelm ; Hofner, Benjamin ; Mayr, Bernhard ; Schöfl, Christof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-71386a5ebd8c6448aa39168e957b7dde607019df74238c04a81f9b0dc51f3cd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alcohol</topic><topic>Alcohols</topic><topic>Allosteric properties</topic><topic>Antagonists</topic><topic>Bartter Syndrome - genetics</topic><topic>Biology and Life Sciences</topic><topic>Calcium</topic><topic>Calcium (blood)</topic><topic>Calcium (extracellular)</topic><topic>Calcium (intracellular)</topic><topic>Calcium - metabolism</topic><topic>Calcium ions</topic><topic>Calcium Signaling - drug effects</topic><topic>Calcium Signaling - genetics</topic><topic>Calcium signalling</topic><topic>Calcium-sensing receptors</topic><topic>Confidence intervals</topic><topic>Diabetes</topic><topic>Drug dosages</topic><topic>Endocrinology</topic><topic>HEK293 Cells</topic><topic>Heterozygosity</topic><topic>Humans</topic><topic>Hypercalciuria</topic><topic>Hypercalciuria - genetics</topic><topic>Hypocalcemia</topic><topic>Hypocalcemia - genetics</topic><topic>Hypoparathyroidism - congenital</topic><topic>Hypoparathyroidism - genetics</topic><topic>Intracellular signalling</topic><topic>Medical treatment</topic><topic>Medicine and Health Sciences</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Naphthalenes - pharmacology</topic><topic>Parathyroid hormone</topic><topic>Patients</topic><topic>Quinazolinone</topic><topic>Quinazolinones - pharmacology</topic><topic>Receptors, Calcium-Sensing - drug effects</topic><topic>Receptors, Calcium-Sensing - genetics</topic><topic>Salts</topic><topic>Signal transduction</topic><topic>Sodium</topic><topic>Vitamin deficiency</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Letz, Saskia</creatorcontrib><creatorcontrib>Haag, Christine</creatorcontrib><creatorcontrib>Schulze, Egbert</creatorcontrib><creatorcontrib>Frank-Raue, Karin</creatorcontrib><creatorcontrib>Raue, Friedhelm</creatorcontrib><creatorcontrib>Hofner, Benjamin</creatorcontrib><creatorcontrib>Mayr, Bernhard</creatorcontrib><creatorcontrib>Schöfl, Christof</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Letz, Saskia</au><au>Haag, Christine</au><au>Schulze, Egbert</au><au>Frank-Raue, Karin</au><au>Raue, Friedhelm</au><au>Hofner, Benjamin</au><au>Mayr, Bernhard</au><au>Schöfl, Christof</au><au>Valenti, Giovanna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-12-15</date><risdate>2014</risdate><volume>9</volume><issue>12</issue><spage>e115178</spage><epage>e115178</epage><pages>e115178-e115178</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Activating calcium sensing receptor (CaSR) mutations cause autosomal dominant hypocalcemia (ADH) characterized by low serum calcium, inappropriately low PTH and relative hypercalciuria. Four activating CaSR mutations cause additional renal wasting of sodium, chloride and other salts, a condition called Bartter syndrome (BS) type 5. Until today there is no specific medical treatment for BS type 5 and ADH. We investigated the effects of different allosteric CaSR antagonists (calcilytics) on activating CaSR mutants.
All 4 known mutations causing BS type 5 and five ADH mutations were expressed in HEK 293T cells and receptor signalling was studied by measurement of intracellular free calcium in response to extracellular calcium ([Ca2+]o). To investigate the effect of calcilytics, cells were stimulated with 3 mM [Ca2+]o in the presence or absence of NPS-2143, ATF936 or AXT914.
All BS type 5 and ADH mutants showed enhanced signalling activity to [Ca2+]o with left shifted dose response curves. In contrast to the amino alcohol NPS-2143, which was only partially effective, the quinazolinone calcilytics ATF936 and AXT914 significantly mitigated excessive cytosolic calcium signalling of all BS type 5 and ADH mutants studied. When these mutants were co-expressed with wild-type CaSR to approximate heterozygosity in patients, ATF936 and AXT914 were also effective on all mutants.
The calcilytics ATF936 and AXT914 are capable of attenuating enhanced cytosolic calcium signalling activity of CaSR mutations causing BS type 5 and ADH. Quinazolinone calcilytics might therefore offer a novel treatment option for patients with activating CaSR mutations.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25506941</pmid><doi>10.1371/journal.pone.0115178</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1636753328 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Alcohol Alcohols Allosteric properties Antagonists Bartter Syndrome - genetics Biology and Life Sciences Calcium Calcium (blood) Calcium (extracellular) Calcium (intracellular) Calcium - metabolism Calcium ions Calcium Signaling - drug effects Calcium Signaling - genetics Calcium signalling Calcium-sensing receptors Confidence intervals Diabetes Drug dosages Endocrinology HEK293 Cells Heterozygosity Humans Hypercalciuria Hypercalciuria - genetics Hypocalcemia Hypocalcemia - genetics Hypoparathyroidism - congenital Hypoparathyroidism - genetics Intracellular signalling Medical treatment Medicine and Health Sciences Mutants Mutation Naphthalenes - pharmacology Parathyroid hormone Patients Quinazolinone Quinazolinones - pharmacology Receptors, Calcium-Sensing - drug effects Receptors, Calcium-Sensing - genetics Salts Signal transduction Sodium Vitamin deficiency |
| title | Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T22%3A47%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Amino%20alcohol-%20(NPS-2143)%20and%20quinazolinone-derived%20calcilytics%20(ATF936%20and%20AXT914)%20differentially%20mitigate%20excessive%20signalling%20of%20calcium-sensing%20receptor%20mutants%20causing%20Bartter%20syndrome%20Type%205%20and%20autosomal%20dominant%20hypocalcemia&rft.jtitle=PloS%20one&rft.au=Letz,%20Saskia&rft.date=2014-12-15&rft.volume=9&rft.issue=12&rft.spage=e115178&rft.epage=e115178&rft.pages=e115178-e115178&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0115178&rft_dat=%3Cproquest_plos_%3E1639486330%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1636753328&rft_id=info:pmid/25506941&rft_doaj_id=oai_doaj_org_article_e1d0764a84934af688578252ec8eb1d4&rfr_iscdi=true |