Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin
Apelin peptides have recently been identified to be the endogenous ligands for the G protein‐coupled receptor APJ. However, little is known about the physiological roles of this ligand‐receptor pairing. In the present study we investigated the pharmacology of several apelin analogues at the human re...
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| Veröffentlicht in: | Journal of neurochemistry 2003-03, Vol.84 (5), p.1162-1172 |
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| creator | Medhurst, Andrew D. Jennings, Carol A. Robbins, Melanie J. Davis, Robert P. Ellis, Catherine Winborn, Kim Y. Lawrie, Kenneth W. M. Hervieu, Guillaume Riley, Graham Bolaky, Jane E. Herrity, Nicole C. Murdock, Paul Darker, John G. |
| description | Apelin peptides have recently been identified to be the endogenous ligands for the G protein‐coupled receptor APJ. However, little is known about the physiological roles of this ligand‐receptor pairing. In the present study we investigated the pharmacology of several apelin analogues at the human recombinant APJ receptor using radioligand binding and functional assays. This has led to the identification of key residues in the apelin peptide required for functional potency and binding affinity through structure–activity studies. In particular, we have identified that replacement of leucine in position 5, or arginine in position 2 and 4 of the C‐terminal apelin peptide, apelin‐13, resulted in significant changes in pharmacology. We also investigated the detailed localization of pre‐proapelin and APJ receptor mRNA in a wide range of human, rat and mouse tissues using quantitative RT–PCR, and carried out a detailed immunohistochemical study of the distribution of the APJ receptor in rat brain and spinal cord. Interestingly, the APJ receptor was not only co‐localized in white matter with GFAP in the spinal cord, but was also clearly localized on neurones in the brain, suggesting that this receptor and its peptide may be involved in a wide range of biological process yet to be determined. |
| doi_str_mv | 10.1046/j.1471-4159.2003.01587.x |
| format | Article |
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M. ; Hervieu, Guillaume ; Riley, Graham ; Bolaky, Jane E. ; Herrity, Nicole C. ; Murdock, Paul ; Darker, John G.</creator><creatorcontrib>Medhurst, Andrew D. ; Jennings, Carol A. ; Robbins, Melanie J. ; Davis, Robert P. ; Ellis, Catherine ; Winborn, Kim Y. ; Lawrie, Kenneth W. M. ; Hervieu, Guillaume ; Riley, Graham ; Bolaky, Jane E. ; Herrity, Nicole C. ; Murdock, Paul ; Darker, John G.</creatorcontrib><description>Apelin peptides have recently been identified to be the endogenous ligands for the G protein‐coupled receptor APJ. However, little is known about the physiological roles of this ligand‐receptor pairing. In the present study we investigated the pharmacology of several apelin analogues at the human recombinant APJ receptor using radioligand binding and functional assays. This has led to the identification of key residues in the apelin peptide required for functional potency and binding affinity through structure–activity studies. In particular, we have identified that replacement of leucine in position 5, or arginine in position 2 and 4 of the C‐terminal apelin peptide, apelin‐13, resulted in significant changes in pharmacology. We also investigated the detailed localization of pre‐proapelin and APJ receptor mRNA in a wide range of human, rat and mouse tissues using quantitative RT–PCR, and carried out a detailed immunohistochemical study of the distribution of the APJ receptor in rat brain and spinal cord. Interestingly, the APJ receptor was not only co‐localized in white matter with GFAP in the spinal cord, but was also clearly localized on neurones in the brain, suggesting that this receptor and its peptide may be involved in a wide range of biological process yet to be determined.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1046/j.1471-4159.2003.01587.x</identifier><identifier>PMID: 12603839</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adipokines ; Amino Acid Substitution ; Animals ; Apelin ; Apelin Receptors ; APJ receptor ; Binding, Competitive - physiology ; Biological and medical sciences ; Blotting, Western ; Brain - metabolism ; Carrier Proteins - biosynthesis ; Carrier Proteins - chemistry ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell Line ; Cell receptors ; Cell structures and functions ; Cyclic AMP - metabolism ; Fluorometry ; Fundamental and applied biological sciences. Psychology ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; Ligands ; Mice ; Miscellaneous ; Molecular and cellular biology ; Mutagenesis, Site-Directed ; Organ Specificity ; Protein Binding - physiology ; Radioligand Assay ; Rats ; Receptors, Dopamine D2 - chemistry ; Receptors, Dopamine D2 - genetics ; Receptors, Dopamine D2 - metabolism ; Receptors, G-Protein-Coupled ; Reverse Transcriptase Polymerase Chain Reaction ; Spinal Cord - metabolism ; Structure-Activity Relationship ; TaqMan</subject><ispartof>Journal of neurochemistry, 2003-03, Vol.84 (5), p.1162-1172</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5427-1f98789f223438da9769675f978b80e735165a68ffa21a28ce6c70dd83df6ded3</citedby><cites>FETCH-LOGICAL-c5427-1f98789f223438da9769675f978b80e735165a68ffa21a28ce6c70dd83df6ded3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1471-4159.2003.01587.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1471-4159.2003.01587.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14546212$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12603839$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Medhurst, Andrew D.</creatorcontrib><creatorcontrib>Jennings, Carol A.</creatorcontrib><creatorcontrib>Robbins, Melanie J.</creatorcontrib><creatorcontrib>Davis, Robert P.</creatorcontrib><creatorcontrib>Ellis, Catherine</creatorcontrib><creatorcontrib>Winborn, Kim Y.</creatorcontrib><creatorcontrib>Lawrie, Kenneth W. M.</creatorcontrib><creatorcontrib>Hervieu, Guillaume</creatorcontrib><creatorcontrib>Riley, Graham</creatorcontrib><creatorcontrib>Bolaky, Jane E.</creatorcontrib><creatorcontrib>Herrity, Nicole C.</creatorcontrib><creatorcontrib>Murdock, Paul</creatorcontrib><creatorcontrib>Darker, John G.</creatorcontrib><title>Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>Apelin peptides have recently been identified to be the endogenous ligands for the G protein‐coupled receptor APJ. However, little is known about the physiological roles of this ligand‐receptor pairing. In the present study we investigated the pharmacology of several apelin analogues at the human recombinant APJ receptor using radioligand binding and functional assays. This has led to the identification of key residues in the apelin peptide required for functional potency and binding affinity through structure–activity studies. In particular, we have identified that replacement of leucine in position 5, or arginine in position 2 and 4 of the C‐terminal apelin peptide, apelin‐13, resulted in significant changes in pharmacology. We also investigated the detailed localization of pre‐proapelin and APJ receptor mRNA in a wide range of human, rat and mouse tissues using quantitative RT–PCR, and carried out a detailed immunohistochemical study of the distribution of the APJ receptor in rat brain and spinal cord. Interestingly, the APJ receptor was not only co‐localized in white matter with GFAP in the spinal cord, but was also clearly localized on neurones in the brain, suggesting that this receptor and its peptide may be involved in a wide range of biological process yet to be determined.</description><subject>Adipokines</subject><subject>Amino Acid Substitution</subject><subject>Animals</subject><subject>Apelin</subject><subject>Apelin Receptors</subject><subject>APJ receptor</subject><subject>Binding, Competitive - physiology</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Brain - metabolism</subject><subject>Carrier Proteins - biosynthesis</subject><subject>Carrier Proteins - chemistry</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Line</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>Cyclic AMP - metabolism</subject><subject>Fluorometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intercellular Signaling Peptides and Proteins</subject><subject>Ligands</subject><subject>Mice</subject><subject>Miscellaneous</subject><subject>Molecular and cellular biology</subject><subject>Mutagenesis, Site-Directed</subject><subject>Organ Specificity</subject><subject>Protein Binding - physiology</subject><subject>Radioligand Assay</subject><subject>Rats</subject><subject>Receptors, Dopamine D2 - chemistry</subject><subject>Receptors, Dopamine D2 - genetics</subject><subject>Receptors, Dopamine D2 - metabolism</subject><subject>Receptors, G-Protein-Coupled</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Spinal Cord - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>TaqMan</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMtu2zAQRYmiReOk_YWAm3YnhS-R1CKLwMijQdBm0a4JhhzaNCTRJWXk8fWRYqPZdsXBzLmcwUEIU1JTIuTZpqZC0UrQpq0ZIbwmtNGqfvqAFv8GH9GCEMYqTgQ7QselbAihUkj6GR1RJgnXvF2g_n5tc29d6tIqOtthO3gc-343pHUsY3Jr6N_6buKsGyHHFzvGNOAU8LgGfHF_izM42I4p78NjwTD4tIIh7Qru4mru2i10cfiCPgXbFfh6eE_Qn6vL38ub6u7X9Y_lxV3lGsFURUOrlW4DY1xw7W2rZCtVE1qlHzQBxRsqGyt1CJZRy7QD6RTxXnMfpAfPT9D3_b_bnP7uoIymj8VB19kBpqMM1ZrIlsgJ1HvQ5VRKhmC2OfY2PxtKzKzabMxs1MxGzazavKk2T1P09LBj99CDfw8e3E7AtwNgy2QwZDu4WN450QjJKJu48z33GDt4_u8DzO3P5VzxVyngmzU</recordid><startdate>200303</startdate><enddate>200303</enddate><creator>Medhurst, Andrew D.</creator><creator>Jennings, Carol A.</creator><creator>Robbins, Melanie J.</creator><creator>Davis, Robert P.</creator><creator>Ellis, Catherine</creator><creator>Winborn, Kim Y.</creator><creator>Lawrie, Kenneth W. M.</creator><creator>Hervieu, Guillaume</creator><creator>Riley, Graham</creator><creator>Bolaky, Jane E.</creator><creator>Herrity, Nicole C.</creator><creator>Murdock, Paul</creator><creator>Darker, John G.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><scope>IQODW</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>7TK</scope></search><sort><creationdate>200303</creationdate><title>Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin</title><author>Medhurst, Andrew D. ; Jennings, Carol A. ; Robbins, Melanie J. ; Davis, Robert P. ; Ellis, Catherine ; Winborn, Kim Y. ; Lawrie, Kenneth W. M. ; Hervieu, Guillaume ; Riley, Graham ; Bolaky, Jane E. ; Herrity, Nicole C. ; Murdock, Paul ; Darker, John G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5427-1f98789f223438da9769675f978b80e735165a68ffa21a28ce6c70dd83df6ded3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adipokines</topic><topic>Amino Acid Substitution</topic><topic>Animals</topic><topic>Apelin</topic><topic>Apelin Receptors</topic><topic>APJ receptor</topic><topic>Binding, Competitive - physiology</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Brain - metabolism</topic><topic>Carrier Proteins - biosynthesis</topic><topic>Carrier Proteins - chemistry</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Line</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>Cyclic AMP - metabolism</topic><topic>Fluorometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intercellular Signaling Peptides and Proteins</topic><topic>Ligands</topic><topic>Mice</topic><topic>Miscellaneous</topic><topic>Molecular and cellular biology</topic><topic>Mutagenesis, Site-Directed</topic><topic>Organ Specificity</topic><topic>Protein Binding - physiology</topic><topic>Radioligand Assay</topic><topic>Rats</topic><topic>Receptors, Dopamine D2 - chemistry</topic><topic>Receptors, Dopamine D2 - genetics</topic><topic>Receptors, Dopamine D2 - metabolism</topic><topic>Receptors, G-Protein-Coupled</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Spinal Cord - metabolism</topic><topic>Structure-Activity Relationship</topic><topic>TaqMan</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Medhurst, Andrew D.</creatorcontrib><creatorcontrib>Jennings, Carol A.</creatorcontrib><creatorcontrib>Robbins, Melanie J.</creatorcontrib><creatorcontrib>Davis, Robert P.</creatorcontrib><creatorcontrib>Ellis, Catherine</creatorcontrib><creatorcontrib>Winborn, Kim Y.</creatorcontrib><creatorcontrib>Lawrie, Kenneth W. 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M.</au><au>Hervieu, Guillaume</au><au>Riley, Graham</au><au>Bolaky, Jane E.</au><au>Herrity, Nicole C.</au><au>Murdock, Paul</au><au>Darker, John G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2003-03</date><risdate>2003</risdate><volume>84</volume><issue>5</issue><spage>1162</spage><epage>1172</epage><pages>1162-1172</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>Apelin peptides have recently been identified to be the endogenous ligands for the G protein‐coupled receptor APJ. However, little is known about the physiological roles of this ligand‐receptor pairing. In the present study we investigated the pharmacology of several apelin analogues at the human recombinant APJ receptor using radioligand binding and functional assays. This has led to the identification of key residues in the apelin peptide required for functional potency and binding affinity through structure–activity studies. In particular, we have identified that replacement of leucine in position 5, or arginine in position 2 and 4 of the C‐terminal apelin peptide, apelin‐13, resulted in significant changes in pharmacology. We also investigated the detailed localization of pre‐proapelin and APJ receptor mRNA in a wide range of human, rat and mouse tissues using quantitative RT–PCR, and carried out a detailed immunohistochemical study of the distribution of the APJ receptor in rat brain and spinal cord. Interestingly, the APJ receptor was not only co‐localized in white matter with GFAP in the spinal cord, but was also clearly localized on neurones in the brain, suggesting that this receptor and its peptide may be involved in a wide range of biological process yet to be determined.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12603839</pmid><doi>10.1046/j.1471-4159.2003.01587.x</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipokines Amino Acid Substitution Animals Apelin Apelin Receptors APJ receptor Binding, Competitive - physiology Biological and medical sciences Blotting, Western Brain - metabolism Carrier Proteins - biosynthesis Carrier Proteins - chemistry Carrier Proteins - genetics Carrier Proteins - metabolism Cell Line Cell receptors Cell structures and functions Cyclic AMP - metabolism Fluorometry Fundamental and applied biological sciences. Psychology Humans Immunohistochemistry Intercellular Signaling Peptides and Proteins Ligands Mice Miscellaneous Molecular and cellular biology Mutagenesis, Site-Directed Organ Specificity Protein Binding - physiology Radioligand Assay Rats Receptors, Dopamine D2 - chemistry Receptors, Dopamine D2 - genetics Receptors, Dopamine D2 - metabolism Receptors, G-Protein-Coupled Reverse Transcriptase Polymerase Chain Reaction Spinal Cord - metabolism Structure-Activity Relationship TaqMan |
| title | Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin |
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