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Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5
Pharmacological and molecular cloning studies have demonstrated heterogeneity of alpha 1-adrenergic receptors. We have now cloned two alpha 1-adrenergic receptors from a rat cerebral cortex cDNA library, using the hamster alpha 1B-adrenergic receptor as a probe. The deduced amino acid sequence of cl...
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Published in: | The Journal of biological chemistry 1991-04, Vol.266 (10), p.6365-6369 |
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creator | Lomasney, J W Cotecchia, S Lorenz, W Leung, W Y Schwinn, D A Yang-Feng, T L Brownstein, M Lefkowitz, R J Caron, M G |
description | Pharmacological and molecular cloning studies have demonstrated heterogeneity of alpha 1-adrenergic receptors. We have now cloned two alpha 1-adrenergic receptors from a rat cerebral cortex cDNA library, using the hamster alpha 1B-adrenergic receptor as a probe. The deduced amino acid sequence of clone RA42 encodes a protein of 560 amino acids whose putative topology is similar to that of the family of G-protein-coupled receptors. The primary structure though most closely resembles that of an alpha 1-adrenergic receptor, having approximately 73% amino acid identity in the putative transmembrane domains with the previously isolated hamster alpha 1B receptor. Analysis of the ligand binding properties of RA42 expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique alpha 1-adrenergic receptor pharmacology. High affinity for the antagonist WB4101 and agonists phenylephrine and methoxamine suggests that cDNA RA42 encodes the alpha 1A receptor subtype. Northern blot analysis of various rat tissues also shows the distribution expected of the alpha 1A receptor subtype with abundant expression in vas deferens followed by hippocampus, cerebral cortex, aorta, brainstem, heart and spleen. The second alpha 1-adrenergic receptor cloned represents the rat homolog of the hamster alpha 1B subtype. Expression of mRNA for this receptor is strongly detected in liver followed by heart, cerebral cortex, brain stem, kidney, lung, and spleen. This study provides definitive evidence for the existence of three alpha 1-adrenergic receptor subtypes. |
doi_str_mv | 10.1016/S0021-9258(18)38126-2 |
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The gene for which is located on human chromosome 5</title><source>ScienceDirect - Connect here FIRST to enable access</source><creator>Lomasney, J W ; Cotecchia, S ; Lorenz, W ; Leung, W Y ; Schwinn, D A ; Yang-Feng, T L ; Brownstein, M ; Lefkowitz, R J ; Caron, M G</creator><creatorcontrib>Lomasney, J W ; Cotecchia, S ; Lorenz, W ; Leung, W Y ; Schwinn, D A ; Yang-Feng, T L ; Brownstein, M ; Lefkowitz, R J ; Caron, M G</creatorcontrib><description>Pharmacological and molecular cloning studies have demonstrated heterogeneity of alpha 1-adrenergic receptors. We have now cloned two alpha 1-adrenergic receptors from a rat cerebral cortex cDNA library, using the hamster alpha 1B-adrenergic receptor as a probe. The deduced amino acid sequence of clone RA42 encodes a protein of 560 amino acids whose putative topology is similar to that of the family of G-protein-coupled receptors. The primary structure though most closely resembles that of an alpha 1-adrenergic receptor, having approximately 73% amino acid identity in the putative transmembrane domains with the previously isolated hamster alpha 1B receptor. Analysis of the ligand binding properties of RA42 expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique alpha 1-adrenergic receptor pharmacology. High affinity for the antagonist WB4101 and agonists phenylephrine and methoxamine suggests that cDNA RA42 encodes the alpha 1A receptor subtype. Northern blot analysis of various rat tissues also shows the distribution expected of the alpha 1A receptor subtype with abundant expression in vas deferens followed by hippocampus, cerebral cortex, aorta, brainstem, heart and spleen. The second alpha 1-adrenergic receptor cloned represents the rat homolog of the hamster alpha 1B subtype. Expression of mRNA for this receptor is strongly detected in liver followed by heart, cerebral cortex, brain stem, kidney, lung, and spleen. This study provides definitive evidence for the existence of three alpha 1-adrenergic receptor subtypes.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(18)38126-2</identifier><identifier>PMID: 1706716</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Animals ; Autoradiography ; Base Sequence ; Blotting, Northern ; Blotting, Southern ; Chromosome Mapping ; Chromosomes, Human, Pair 5 ; Cloning, Molecular ; DNA - genetics ; Gene Expression Regulation ; Humans ; Molecular Sequence Data ; Plasmids ; Rats ; Receptors, Adrenergic, alpha - genetics ; Restriction Mapping ; RNA - analysis</subject><ispartof>The Journal of biological chemistry, 1991-04, Vol.266 (10), p.6365-6369</ispartof><rights>1991 © 1991 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-19bdb3341d62c12d6b21e5d12df977c14d592b22bf37826bdea357668072240b3</citedby><cites>FETCH-LOGICAL-c433t-19bdb3341d62c12d6b21e5d12df977c14d592b22bf37826bdea357668072240b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021925818381262$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3549,27924,27925,45780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1706716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lomasney, J W</creatorcontrib><creatorcontrib>Cotecchia, S</creatorcontrib><creatorcontrib>Lorenz, W</creatorcontrib><creatorcontrib>Leung, W Y</creatorcontrib><creatorcontrib>Schwinn, D A</creatorcontrib><creatorcontrib>Yang-Feng, T L</creatorcontrib><creatorcontrib>Brownstein, M</creatorcontrib><creatorcontrib>Lefkowitz, R J</creatorcontrib><creatorcontrib>Caron, M G</creatorcontrib><title>Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Pharmacological and molecular cloning studies have demonstrated heterogeneity of alpha 1-adrenergic receptors. We have now cloned two alpha 1-adrenergic receptors from a rat cerebral cortex cDNA library, using the hamster alpha 1B-adrenergic receptor as a probe. The deduced amino acid sequence of clone RA42 encodes a protein of 560 amino acids whose putative topology is similar to that of the family of G-protein-coupled receptors. The primary structure though most closely resembles that of an alpha 1-adrenergic receptor, having approximately 73% amino acid identity in the putative transmembrane domains with the previously isolated hamster alpha 1B receptor. Analysis of the ligand binding properties of RA42 expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique alpha 1-adrenergic receptor pharmacology. High affinity for the antagonist WB4101 and agonists phenylephrine and methoxamine suggests that cDNA RA42 encodes the alpha 1A receptor subtype. Northern blot analysis of various rat tissues also shows the distribution expected of the alpha 1A receptor subtype with abundant expression in vas deferens followed by hippocampus, cerebral cortex, aorta, brainstem, heart and spleen. The second alpha 1-adrenergic receptor cloned represents the rat homolog of the hamster alpha 1B subtype. Expression of mRNA for this receptor is strongly detected in liver followed by heart, cerebral cortex, brain stem, kidney, lung, and spleen. This study provides definitive evidence for the existence of three alpha 1-adrenergic receptor subtypes.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Autoradiography</subject><subject>Base Sequence</subject><subject>Blotting, Northern</subject><subject>Blotting, Southern</subject><subject>Chromosome Mapping</subject><subject>Chromosomes, Human, Pair 5</subject><subject>Cloning, Molecular</subject><subject>DNA - genetics</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>Plasmids</subject><subject>Rats</subject><subject>Receptors, Adrenergic, alpha - genetics</subject><subject>Restriction Mapping</subject><subject>RNA - analysis</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><recordid>eNqFkMFu1DAQhi0EKtvCI1SyhITgkOKxEyc5oVWhUKnAgSJxsxx7sjFK4tROaHmBPjfeTUWP-GKP5_vH1kfIKbAzYCDffWeMQ1bzonoD1VtRAZcZf0I2wCqRiQJ-PiWbf8hzchzjL5ZWXsMROYKSyRLkhtx_8T2apdeBmt6PbtxRPVqKd1PAGJ0fqW_p3CE1H75uaevDodD91GkK20zbgCOGnTM0oMFp9uGMXidil64P-G3nTEddpL03ekZL08huGfRITRf84KMfkBYvyLNW9xFfPuwn5MfFx-vzz9nVt0-X59urzORCzBnUjW2EyMFKboBb2XDAwqZTW5elgdwWNW84b1pRVlw2FrUoSikrVnKes0ackNfr3Cn4mwXjrAYXDfa9HtEvUVUsr2peygQWK2iCjzFgq6bgBh3-KGBq718d_Ku9XAWVOvhXPOVOHx5YmgHtY2oVnvqv1n7ndt2tC6ga502Hg-JS7mdLIYtEvV8pTC5-OwwqGoejQZsSZlbWu__84y-y7qAn</recordid><startdate>19910405</startdate><enddate>19910405</enddate><creator>Lomasney, J W</creator><creator>Cotecchia, S</creator><creator>Lorenz, W</creator><creator>Leung, W Y</creator><creator>Schwinn, D A</creator><creator>Yang-Feng, T L</creator><creator>Brownstein, M</creator><creator>Lefkowitz, R J</creator><creator>Caron, M G</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>19910405</creationdate><title>Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5</title><author>Lomasney, J W ; Cotecchia, S ; Lorenz, W ; Leung, W Y ; Schwinn, D A ; Yang-Feng, T L ; Brownstein, M ; Lefkowitz, R J ; Caron, M G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-19bdb3341d62c12d6b21e5d12df977c14d592b22bf37826bdea357668072240b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Autoradiography</topic><topic>Base Sequence</topic><topic>Blotting, Northern</topic><topic>Blotting, Southern</topic><topic>Chromosome Mapping</topic><topic>Chromosomes, Human, Pair 5</topic><topic>Cloning, Molecular</topic><topic>DNA - genetics</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Molecular Sequence Data</topic><topic>Plasmids</topic><topic>Rats</topic><topic>Receptors, Adrenergic, alpha - genetics</topic><topic>Restriction Mapping</topic><topic>RNA - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lomasney, J W</creatorcontrib><creatorcontrib>Cotecchia, S</creatorcontrib><creatorcontrib>Lorenz, W</creatorcontrib><creatorcontrib>Leung, W Y</creatorcontrib><creatorcontrib>Schwinn, D A</creatorcontrib><creatorcontrib>Yang-Feng, T L</creatorcontrib><creatorcontrib>Brownstein, M</creatorcontrib><creatorcontrib>Lefkowitz, R J</creatorcontrib><creatorcontrib>Caron, M G</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lomasney, J W</au><au>Cotecchia, S</au><au>Lorenz, W</au><au>Leung, W Y</au><au>Schwinn, D A</au><au>Yang-Feng, T L</au><au>Brownstein, M</au><au>Lefkowitz, R J</au><au>Caron, M G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1991-04-05</date><risdate>1991</risdate><volume>266</volume><issue>10</issue><spage>6365</spage><epage>6369</epage><pages>6365-6369</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Pharmacological and molecular cloning studies have demonstrated heterogeneity of alpha 1-adrenergic receptors. We have now cloned two alpha 1-adrenergic receptors from a rat cerebral cortex cDNA library, using the hamster alpha 1B-adrenergic receptor as a probe. The deduced amino acid sequence of clone RA42 encodes a protein of 560 amino acids whose putative topology is similar to that of the family of G-protein-coupled receptors. The primary structure though most closely resembles that of an alpha 1-adrenergic receptor, having approximately 73% amino acid identity in the putative transmembrane domains with the previously isolated hamster alpha 1B receptor. Analysis of the ligand binding properties of RA42 expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique alpha 1-adrenergic receptor pharmacology. High affinity for the antagonist WB4101 and agonists phenylephrine and methoxamine suggests that cDNA RA42 encodes the alpha 1A receptor subtype. Northern blot analysis of various rat tissues also shows the distribution expected of the alpha 1A receptor subtype with abundant expression in vas deferens followed by hippocampus, cerebral cortex, aorta, brainstem, heart and spleen. The second alpha 1-adrenergic receptor cloned represents the rat homolog of the hamster alpha 1B subtype. 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subjects | Amino Acid Sequence Animals Autoradiography Base Sequence Blotting, Northern Blotting, Southern Chromosome Mapping Chromosomes, Human, Pair 5 Cloning, Molecular DNA - genetics Gene Expression Regulation Humans Molecular Sequence Data Plasmids Rats Receptors, Adrenergic, alpha - genetics Restriction Mapping RNA - analysis |
title | Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5 |
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