Pharmacological and molecular characterization of 5-hydroxytryptamine(7) receptors in the rat adrenal gland
Serotonin (5-hydroxytryptamine; 5-HT) is a potent stimulator of aldosterone secretion in the rat adrenal gland but the type of receptor involved in the mechanism of action of 5-HT remains unknown. The aim of the present study was to determine the pharmacological profile and to clone the receptor res...
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| Veröffentlicht in: | Molecular pharmacology 1999-09, Vol.56 (3), p.552-561 |
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| creator | Contesse, V Lenglet, S Grumolato, L Anouar, Y Lihrmann, I Lefebvre, H Delarue, C Vaudry, H |
| description | Serotonin (5-hydroxytryptamine; 5-HT) is a potent stimulator of aldosterone secretion in the rat adrenal gland but the type of receptor involved in the mechanism of action of 5-HT remains unknown. The aim of the present study was to determine the pharmacological profile and to clone the receptor responsible for the corticotropic effect of 5-HT in rat glomerulosa cells. A series of 10 serotonergic receptor agonists and 12 receptor antagonists was used to characterize the receptor mediating the effect of 5-HT on aldosterone secretion from perifused rat adrenocortical slices. Correlation analysis between the potencies of the different compounds in our model and those previously reported for various recombinant 5-HT receptors showed that the rat adrenal 5-HT receptor exhibits the same pharmacological profile as the 5-HT(7) receptor transiently expressed in COS-7 cells (r = 0.82 for agonists, p |
| doi_str_mv | 10.1124/mol.56.3.552 |
| format | Article |
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The aim of the present study was to determine the pharmacological profile and to clone the receptor responsible for the corticotropic effect of 5-HT in rat glomerulosa cells. A series of 10 serotonergic receptor agonists and 12 receptor antagonists was used to characterize the receptor mediating the effect of 5-HT on aldosterone secretion from perifused rat adrenocortical slices. Correlation analysis between the potencies of the different compounds in our model and those previously reported for various recombinant 5-HT receptors showed that the rat adrenal 5-HT receptor exhibits the same pharmacological profile as the 5-HT(7) receptor transiently expressed in COS-7 cells (r = 0.82 for agonists, p <.05; r = 0.83 for antagonists, p <.01). Polymerase chain reaction with specific primers revealed the expression of 5-HT(7) receptor mRNA in the rat adrenal gland. Cloning of the polymerase chain reaction product confirmed that the amplified DNA corresponded to the 5-HT(7) receptor cDNA sequence. Western blot analysis showed the presence of a protein with an apparent molecular mass of 66 kDa in the adrenal cortex but not in the medulla. Taken together, these data demonstrate that the rat adrenal glomerulosa expresses functional 5-HT(7) receptors. Rat glomerulosa cells will thus provide a robust and sensitive bioassay for future studies on native 5-HT(7) receptors.</description><identifier>ISSN: 0026-895X</identifier><identifier>DOI: 10.1124/mol.56.3.552</identifier><identifier>PMID: 10462543</identifier><language>eng</language><publisher>United States</publisher><subject>Adrenal Glands - drug effects ; Adrenal Glands - metabolism ; Aldosterone - metabolism ; Animals ; Blotting, Western ; Male ; Rats ; Rats, Wistar ; Receptors, Serotonin - drug effects ; Receptors, Serotonin - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Serotonin Antagonists - pharmacology ; Serotonin Receptor Agonists - pharmacology</subject><ispartof>Molecular pharmacology, 1999-09, Vol.56 (3), p.552-561</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10462543$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Contesse, V</creatorcontrib><creatorcontrib>Lenglet, S</creatorcontrib><creatorcontrib>Grumolato, L</creatorcontrib><creatorcontrib>Anouar, Y</creatorcontrib><creatorcontrib>Lihrmann, I</creatorcontrib><creatorcontrib>Lefebvre, H</creatorcontrib><creatorcontrib>Delarue, C</creatorcontrib><creatorcontrib>Vaudry, H</creatorcontrib><title>Pharmacological and molecular characterization of 5-hydroxytryptamine(7) receptors in the rat adrenal gland</title><title>Molecular pharmacology</title><addtitle>Mol Pharmacol</addtitle><description>Serotonin (5-hydroxytryptamine; 5-HT) is a potent stimulator of aldosterone secretion in the rat adrenal gland but the type of receptor involved in the mechanism of action of 5-HT remains unknown. The aim of the present study was to determine the pharmacological profile and to clone the receptor responsible for the corticotropic effect of 5-HT in rat glomerulosa cells. A series of 10 serotonergic receptor agonists and 12 receptor antagonists was used to characterize the receptor mediating the effect of 5-HT on aldosterone secretion from perifused rat adrenocortical slices. Correlation analysis between the potencies of the different compounds in our model and those previously reported for various recombinant 5-HT receptors showed that the rat adrenal 5-HT receptor exhibits the same pharmacological profile as the 5-HT(7) receptor transiently expressed in COS-7 cells (r = 0.82 for agonists, p <.05; r = 0.83 for antagonists, p <.01). Polymerase chain reaction with specific primers revealed the expression of 5-HT(7) receptor mRNA in the rat adrenal gland. Cloning of the polymerase chain reaction product confirmed that the amplified DNA corresponded to the 5-HT(7) receptor cDNA sequence. Western blot analysis showed the presence of a protein with an apparent molecular mass of 66 kDa in the adrenal cortex but not in the medulla. Taken together, these data demonstrate that the rat adrenal glomerulosa expresses functional 5-HT(7) receptors. Rat glomerulosa cells will thus provide a robust and sensitive bioassay for future studies on native 5-HT(7) receptors.</description><subject>Adrenal Glands - drug effects</subject><subject>Adrenal Glands - metabolism</subject><subject>Aldosterone - metabolism</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Male</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Serotonin - drug effects</subject><subject>Receptors, Serotonin - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Serotonin Antagonists - pharmacology</subject><subject>Serotonin Receptor Agonists - pharmacology</subject><issn>0026-895X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo10D1PwzAQBmAPIFoKGzPyhGBI8HebEVXlQ6oEA0hskXN22kASB9uRCL8eS5Rb3uFePTodQheU5JQycdu5Npcq57mU7AjNCWEqWxXyfYZOQ_gghAq5IidoRolQTAo-R58ve-07Da51uwZ0i3VvcGIsjK32GNJWQ7S--dGxcT12NZbZfjLefU_RT0PUXdPb6-UN9hbsEJ0PuOlx3FvsdcTaeNsnddcm9wwd17oN9vyQC_R2v3ldP2bb54en9d02GygvYmZMJeyqNswwQg2BiqmCggWha8mhVtUSloRAXSvBGUgwghNOWUWoopxLyRfo6s8dvPsabYhl1wSwbbrBujGUqkiTiFS8PBTHqrOmHHzTaT-V_-_hvybLZuc</recordid><startdate>199909</startdate><enddate>199909</enddate><creator>Contesse, V</creator><creator>Lenglet, S</creator><creator>Grumolato, L</creator><creator>Anouar, Y</creator><creator>Lihrmann, I</creator><creator>Lefebvre, H</creator><creator>Delarue, C</creator><creator>Vaudry, H</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>199909</creationdate><title>Pharmacological and molecular characterization of 5-hydroxytryptamine(7) receptors in the rat adrenal gland</title><author>Contesse, V ; Lenglet, S ; Grumolato, L ; Anouar, Y ; Lihrmann, I ; Lefebvre, H ; Delarue, C ; Vaudry, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p139t-ddb4e8fd2d201d0cb2691cec4af53cf6b7c700cff6432c5cd430312b016133553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adrenal Glands - drug effects</topic><topic>Adrenal Glands - metabolism</topic><topic>Aldosterone - metabolism</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Male</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Serotonin - drug effects</topic><topic>Receptors, Serotonin - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Serotonin Antagonists - pharmacology</topic><topic>Serotonin Receptor Agonists - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Contesse, V</creatorcontrib><creatorcontrib>Lenglet, S</creatorcontrib><creatorcontrib>Grumolato, L</creatorcontrib><creatorcontrib>Anouar, Y</creatorcontrib><creatorcontrib>Lihrmann, I</creatorcontrib><creatorcontrib>Lefebvre, H</creatorcontrib><creatorcontrib>Delarue, C</creatorcontrib><creatorcontrib>Vaudry, H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Contesse, V</au><au>Lenglet, S</au><au>Grumolato, L</au><au>Anouar, Y</au><au>Lihrmann, I</au><au>Lefebvre, H</au><au>Delarue, C</au><au>Vaudry, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacological and molecular characterization of 5-hydroxytryptamine(7) receptors in the rat adrenal gland</atitle><jtitle>Molecular pharmacology</jtitle><addtitle>Mol Pharmacol</addtitle><date>1999-09</date><risdate>1999</risdate><volume>56</volume><issue>3</issue><spage>552</spage><epage>561</epage><pages>552-561</pages><issn>0026-895X</issn><abstract>Serotonin (5-hydroxytryptamine; 5-HT) is a potent stimulator of aldosterone secretion in the rat adrenal gland but the type of receptor involved in the mechanism of action of 5-HT remains unknown. The aim of the present study was to determine the pharmacological profile and to clone the receptor responsible for the corticotropic effect of 5-HT in rat glomerulosa cells. A series of 10 serotonergic receptor agonists and 12 receptor antagonists was used to characterize the receptor mediating the effect of 5-HT on aldosterone secretion from perifused rat adrenocortical slices. Correlation analysis between the potencies of the different compounds in our model and those previously reported for various recombinant 5-HT receptors showed that the rat adrenal 5-HT receptor exhibits the same pharmacological profile as the 5-HT(7) receptor transiently expressed in COS-7 cells (r = 0.82 for agonists, p <.05; r = 0.83 for antagonists, p <.01). Polymerase chain reaction with specific primers revealed the expression of 5-HT(7) receptor mRNA in the rat adrenal gland. Cloning of the polymerase chain reaction product confirmed that the amplified DNA corresponded to the 5-HT(7) receptor cDNA sequence. Western blot analysis showed the presence of a protein with an apparent molecular mass of 66 kDa in the adrenal cortex but not in the medulla. Taken together, these data demonstrate that the rat adrenal glomerulosa expresses functional 5-HT(7) receptors. Rat glomerulosa cells will thus provide a robust and sensitive bioassay for future studies on native 5-HT(7) receptors.</abstract><cop>United States</cop><pmid>10462543</pmid><doi>10.1124/mol.56.3.552</doi><tpages>10</tpages></addata></record> |
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| subjects | Adrenal Glands - drug effects Adrenal Glands - metabolism Aldosterone - metabolism Animals Blotting, Western Male Rats Rats, Wistar Receptors, Serotonin - drug effects Receptors, Serotonin - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Serotonin Antagonists - pharmacology Serotonin Receptor Agonists - pharmacology |
| title | Pharmacological and molecular characterization of 5-hydroxytryptamine(7) receptors in the rat adrenal gland |
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