Murine GPRC6A Mediates Cellular Responses to L-Amino Acids, but Not Osteocalcin Variants.
Identifieur interne : 002328 ( PubMed/Curation ); précédent : 002327; suivant : 002329Murine GPRC6A Mediates Cellular Responses to L-Amino Acids, but Not Osteocalcin Variants.
Auteurs : Patricia Rueda [Australie] ; Elizabeth Harley [France] ; Yao Lu [Australie] ; Gregory D. Stewart [Australie] ; Stewart Fabb [Australie] ; Natalie Diepenhorst [Australie] ; Béatrice Cremers [France] ; Marie-Hélène Rouillon [France] ; Isabelle Wehrle [France] ; Anne Geant [France] ; Gwladys Lamarche [France] ; Katie Leach [Australie] ; William N. Charman [Australie] ; Arthur Christopoulos [Australie] ; Roger J. Summers [Australie] ; Patrick M. Sexton [Australie] ; Christopher J. Langmead [Australie]Source :
- PloS one [ 1932-6203 ] ; 2016.
Descripteurs français
- KwdFr :
- MESH :
- métabolisme : Cellules à insuline, Glucagon-like peptide 1, Insuline, Récepteurs couplés aux protéines G.
- pharmacologie : Acides aminés, Ostéocalcine.
- Animaux, Cellules HEK293, Cellules à insuline, Humains, Liaison aux protéines, Souris.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Glucagon-Like Peptide 1, Insulin, Receptors, G-Protein-Coupled.
- chemical , pharmacology : Amino Acids, Osteocalcin.
- drug effects : Insulin-Secreting Cells.
- metabolism : Insulin-Secreting Cells.
- Animals, HEK293 Cells, Humans, Mice, Protein Binding.
Abstract
Phenotyping of Gprc6a KO mice has shown that this promiscuous class C G protein coupled receptor is variously involved in regulation of metabolism, inflammation and endocrine function. Such effects are described as mediated by extracellular calcium, L-amino acids, the bone-derived peptide osteocalcin (OCN) and the male hormone testosterone, introducing the concept of a bone-energy-metabolism-reproduction functional crosstalk mediated by GPRC6A. However, whilst the calcium and L-amino acid-sensing properties of GPRC6A are well established, verification of activity of osteocalcin at both human and mouse GPRC6A in vitro has proven somewhat elusive. This study characterises the in vitro pharmacology of mouse GPRC6A in response to its putative ligands in both recombinant and endogenous GPRC6A-expressing cells. Using cell signalling, and glucagon-like peptide (GLP)-1 and insulin release assays, our results confirm that basic L-amino acids act as agonists of the murine GPRC6A receptor in both recombinant cells and immortalised entero-endocrine and pancreatic β-cells. In contrast, our studies do not support a role for OCN as a direct ligand for mouse GPRC6A, suggesting that the reported in vivo effects of OCN that require GPRC6A may be indirect, rather than via direct activation of the receptor.
DOI: 10.1371/journal.pone.0146846
PubMed: 26785252
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Stewart</name><affiliation wicri:level="1"><nlm:affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea></affiliation></author><author><name sortKey="Fabb, Stewart" sort="Fabb, Stewart" uniqKey="Fabb S" first="Stewart" last="Fabb">Stewart Fabb</name><affiliation wicri:level="1"><nlm:affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea></affiliation></author><author><name sortKey="Diepenhorst, Natalie" sort="Diepenhorst, Natalie" uniqKey="Diepenhorst N" first="Natalie" last="Diepenhorst">Natalie Diepenhorst</name><affiliation wicri:level="1"><nlm:affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea></affiliation></author><author><name sortKey="Cremers, Beatrice" sort="Cremers, Beatrice" uniqKey="Cremers B" first="Béatrice" last="Cremers">Béatrice Cremers</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier, Suresnes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier, Suresnes</wicri:regionArea></affiliation></author><author><name sortKey="Rouillon, Marie Helene" sort="Rouillon, Marie Helene" uniqKey="Rouillon M" first="Marie-Hélène" last="Rouillon">Marie-Hélène Rouillon</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier, Suresnes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier, Suresnes</wicri:regionArea></affiliation></author><author><name sortKey="Wehrle, Isabelle" sort="Wehrle, Isabelle" uniqKey="Wehrle I" first="Isabelle" last="Wehrle">Isabelle Wehrle</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier, Suresnes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier, Suresnes</wicri:regionArea></affiliation></author><author><name sortKey="Geant, Anne" sort="Geant, Anne" uniqKey="Geant A" first="Anne" last="Geant">Anne Geant</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier, Suresnes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier, Suresnes</wicri:regionArea></affiliation></author><author><name sortKey="Lamarche, Gwladys" sort="Lamarche, Gwladys" uniqKey="Lamarche G" first="Gwladys" last="Lamarche">Gwladys Lamarche</name><affiliation wicri:level="1"><nlm:affiliation>Institut de Recherches Servier, Suresnes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherches Servier, Suresnes</wicri:regionArea></affiliation></author><author><name sortKey="Leach, Katie" sort="Leach, Katie" uniqKey="Leach K" first="Katie" last="Leach">Katie Leach</name><affiliation wicri:level="1"><nlm:affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea></affiliation></author><author><name sortKey="Charman, William N" sort="Charman, William N" uniqKey="Charman W" first="William N" last="Charman">William N. Charman</name><affiliation wicri:level="1"><nlm:affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea></affiliation></author><author><name sortKey="Christopoulos, Arthur" sort="Christopoulos, Arthur" uniqKey="Christopoulos A" first="Arthur" last="Christopoulos">Arthur Christopoulos</name><affiliation wicri:level="1"><nlm:affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea></affiliation></author><author><name sortKey="Summers, Roger J" sort="Summers, Roger J" uniqKey="Summers R" first="Roger J" last="Summers">Roger J. Summers</name><affiliation wicri:level="1"><nlm:affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea></affiliation></author><author><name sortKey="Sexton, Patrick M" sort="Sexton, Patrick M" uniqKey="Sexton P" first="Patrick M" last="Sexton">Patrick M. Sexton</name><affiliation wicri:level="1"><nlm:affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea></affiliation></author><author><name sortKey="Langmead, Christopher J" sort="Langmead, Christopher J" uniqKey="Langmead C" first="Christopher J" last="Langmead">Christopher J. Langmead</name><affiliation wicri:level="1"><nlm:affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052</wicri:regionArea></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acids (pharmacology)</term><term>Animals</term><term>Glucagon-Like Peptide 1 (metabolism)</term><term>HEK293 Cells</term><term>Humans</term><term>Insulin (metabolism)</term><term>Insulin-Secreting Cells (drug effects)</term><term>Insulin-Secreting Cells (metabolism)</term><term>Mice</term><term>Osteocalcin (pharmacology)</term><term>Protein Binding</term><term>Receptors, G-Protein-Coupled (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acides aminés (pharmacologie)</term><term>Animaux</term><term>Cellules HEK293</term><term>Cellules à insuline ()</term><term>Cellules à insuline (métabolisme)</term><term>Glucagon-like peptide 1 (métabolisme)</term><term>Humains</term><term>Insuline (métabolisme)</term><term>Liaison aux protéines</term><term>Ostéocalcine (pharmacologie)</term><term>Récepteurs couplés aux protéines G (métabolisme)</term><term>Souris</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glucagon-Like Peptide 1</term><term>Insulin</term><term>Receptors, G-Protein-Coupled</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Amino Acids</term><term>Osteocalcin</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Insulin-Secreting Cells</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Insulin-Secreting Cells</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules à insuline</term><term>Glucagon-like peptide 1</term><term>Insuline</term><term>Récepteurs couplés aux protéines G</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acides aminés</term><term>Ostéocalcine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>HEK293 Cells</term><term>Humans</term><term>Mice</term><term>Protein Binding</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Cellules à insuline</term><term>Humains</term><term>Liaison aux protéines</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Phenotyping of Gprc6a KO mice has shown that this promiscuous class C G protein coupled receptor is variously involved in regulation of metabolism, inflammation and endocrine function. Such effects are described as mediated by extracellular calcium, L-amino acids, the bone-derived peptide osteocalcin (OCN) and the male hormone testosterone, introducing the concept of a bone-energy-metabolism-reproduction functional crosstalk mediated by GPRC6A. However, whilst the calcium and L-amino acid-sensing properties of GPRC6A are well established, verification of activity of osteocalcin at both human and mouse GPRC6A in vitro has proven somewhat elusive. This study characterises the in vitro pharmacology of mouse GPRC6A in response to its putative ligands in both recombinant and endogenous GPRC6A-expressing cells. Using cell signalling, and glucagon-like peptide (GLP)-1 and insulin release assays, our results confirm that basic L-amino acids act as agonists of the murine GPRC6A receptor in both recombinant cells and immortalised entero-endocrine and pancreatic β-cells. In contrast, our studies do not support a role for OCN as a direct ligand for mouse GPRC6A, suggesting that the reported in vivo effects of OCN that require GPRC6A may be indirect, rather than via direct activation of the receptor.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26785252</PMID><DateCreated><Year>2016</Year><Month>01</Month><Day>20</Day></DateCreated><DateCompleted><Year>2016</Year><Month>07</Month><Day>26</Day></DateCompleted><DateRevised><Year>2016</Year><Month>01</Month><Day>31</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>11</Volume><Issue>1</Issue><PubDate><Year>2016</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS ONE</ISOAbbreviation></Journal><ArticleTitle>Murine GPRC6A Mediates Cellular Responses to L-Amino Acids, but Not Osteocalcin Variants.</ArticleTitle><Pagination><MedlinePgn>e0146846</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0146846</ELocationID><Abstract><AbstractText>Phenotyping of Gprc6a KO mice has shown that this promiscuous class C G protein coupled receptor is variously involved in regulation of metabolism, inflammation and endocrine function. Such effects are described as mediated by extracellular calcium, L-amino acids, the bone-derived peptide osteocalcin (OCN) and the male hormone testosterone, introducing the concept of a bone-energy-metabolism-reproduction functional crosstalk mediated by GPRC6A. However, whilst the calcium and L-amino acid-sensing properties of GPRC6A are well established, verification of activity of osteocalcin at both human and mouse GPRC6A in vitro has proven somewhat elusive. This study characterises the in vitro pharmacology of mouse GPRC6A in response to its putative ligands in both recombinant and endogenous GPRC6A-expressing cells. Using cell signalling, and glucagon-like peptide (GLP)-1 and insulin release assays, our results confirm that basic L-amino acids act as agonists of the murine GPRC6A receptor in both recombinant cells and immortalised entero-endocrine and pancreatic β-cells. In contrast, our studies do not support a role for OCN as a direct ligand for mouse GPRC6A, suggesting that the reported in vivo effects of OCN that require GPRC6A may be indirect, rather than via direct activation of the receptor.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rueda</LastName><ForeName>Patricia</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harley</LastName><ForeName>Elizabeth</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Institut de Recherches Servier, Suresnes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Yao</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stewart</LastName><ForeName>Gregory D</ForeName><Initials>GD</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fabb</LastName><ForeName>Stewart</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diepenhorst</LastName><ForeName>Natalie</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cremers</LastName><ForeName>Béatrice</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Institut de Recherches Servier, Suresnes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rouillon</LastName><ForeName>Marie-Hélène</ForeName><Initials>MH</Initials><AffiliationInfo><Affiliation>Institut de Recherches Servier, Suresnes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wehrle</LastName><ForeName>Isabelle</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Institut de Recherches Servier, Suresnes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Geant</LastName><ForeName>Anne</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institut de Recherches Servier, Suresnes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lamarche</LastName><ForeName>Gwladys</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Institut de Recherches Servier, Suresnes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leach</LastName><ForeName>Katie</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Charman</LastName><ForeName>William N</ForeName><Initials>WN</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Christopoulos</LastName><ForeName>Arthur</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Summers</LastName><ForeName>Roger J</ForeName><Initials>RJ</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sexton</LastName><ForeName>Patrick M</ForeName><Initials>PM</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Langmead</LastName><ForeName>Christopher J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>01</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000596">Amino Acids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C515750">GPRC6A protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007328">Insulin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D043562">Receptors, G-Protein-Coupled</NameOfSubstance></Chemical><Chemical><RegistryNumber>104982-03-8</RegistryNumber><NameOfSubstance UI="D015675">Osteocalcin</NameOfSubstance></Chemical><Chemical><RegistryNumber>89750-14-1</RegistryNumber><NameOfSubstance UI="D052216">Glucagon-Like Peptide 1</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Biochemistry. 1995 Jul 25;34(29):9541-51</RefSource><PMID Version="1">7626624</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Physiol Rev. 1989 Jul;69(3):990-1047</RefSource><PMID Version="1">2664828</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mol Pharmacol. 2005 Mar;67(3):589-97</RefSource><PMID Version="1">15576628</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurochem. 2005 Apr;93(2):383-91</RefSource><PMID 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MajorTopicYN="N">Insulin</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050417" MajorTopicYN="N">Insulin-Secreting Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015675" MajorTopicYN="N">Osteocalcin</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D043562" MajorTopicYN="N">Receptors, G-Protein-Coupled</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4718634</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>08</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>12</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>1</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>1</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>7</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26785252</ArticleId><ArticleId IdType="doi">10.1371/journal.pone.0146846</ArticleId><ArticleId IdType="pii">PONE-D-15-36847</ArticleId><ArticleId IdType="pmc">PMC4718634</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce 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