Guanyl Nucleotides Modulate Binding to Steroid Receptors in Neuronal Membranes
The recently characterized corticosteroid receptor on amphibian neuronal membranes appears to mediate rapid, stress-induced changes in male reproductive behaviors. Because the transduction mechanisms associated with this receptor are unknown, we performed radioligand binding studies to determine whe...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1992-05, Vol.89 (9), p.3830-3834 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Orchinik, Miles Murray, Thomas F. Franklin, Paul H. Moore, Frank L. |
| description | The recently characterized corticosteroid receptor on amphibian neuronal membranes appears to mediate rapid, stress-induced changes in male reproductive behaviors. Because the transduction mechanisms associated with this receptor are unknown, we performed radioligand binding studies to determine whether this steroid receptor is negatively modulated by guanyl nucleotides. The binding of [3H] corticosterone to neuronal membranes was inhibited by nonhydrolyzable guanyl nucleotides in both equilibrium saturation binding and titration studies. The addition of guanyl nucleotide plus unlabeled corticosterone induced a rapid phase of[3H] corticosterone dissociation from membranes that was not induced by addition of unlabeled ligand alone. Furthermore, the equilibrium binding of [3H] corticosterone and the sensitivity of the receptor to modulation by guanyl nucleotides were both enhanced by Mg2+. These results are consistent with the formation of a ternary complex of steroid, receptor, and guanine nucleotide-binding protein that is subject to regulation by guanyl nucleotides. Therefore, rapid signal transduction through corticosteroid receptors on neuronal membranes appears to be mediated by guanine nucleotide-binding proteins. |
| doi_str_mv | 10.1073/pnas.89.9.3830 |
| format | Article |
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Because the transduction mechanisms associated with this receptor are unknown, we performed radioligand binding studies to determine whether this steroid receptor is negatively modulated by guanyl nucleotides. The binding of [3H] corticosterone to neuronal membranes was inhibited by nonhydrolyzable guanyl nucleotides in both equilibrium saturation binding and titration studies. The addition of guanyl nucleotide plus unlabeled corticosterone induced a rapid phase of[3H] corticosterone dissociation from membranes that was not induced by addition of unlabeled ligand alone. Furthermore, the equilibrium binding of [3H] corticosterone and the sensitivity of the receptor to modulation by guanyl nucleotides were both enhanced by Mg2+. These results are consistent with the formation of a ternary complex of steroid, receptor, and guanine nucleotide-binding protein that is subject to regulation by guanyl nucleotides. Therefore, rapid signal transduction through corticosteroid receptors on neuronal membranes appears to be mediated by guanine nucleotide-binding proteins.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.89.9.3830</identifier><identifier>PMID: 1570300</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Agonists ; Animals ; binding ; Brain ; Brain - metabolism ; Cell Membrane - metabolism ; Cellular biology ; Corticosteroids ; corticosterone ; Corticosterone - metabolism ; Dithiothreitol - pharmacology ; GTP-Binding Proteins - metabolism ; guanine nucleotides ; Guanine Nucleotides - metabolism ; Ligands ; Magnesium Chloride - pharmacology ; membranes ; modulation ; Nervous system ; neurons ; Neurons - metabolism ; Nuclear membrane ; Nucleotides ; P branes ; Receptors ; Receptors, Glucocorticoid - metabolism ; Salamandridae ; Signal Transduction ; Steroid receptors ; Steroids ; Taricha granulosa</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1992-05, Vol.89 (9), p.3830-3834</ispartof><rights>Copyright 1992 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences May 1, 1992</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c582t-be0b10850ea3d5807e219f14c680728fade5a080ee352cda17a66eef211de9933</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/89/9.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2359759$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2359759$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1570300$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Orchinik, Miles</creatorcontrib><creatorcontrib>Murray, Thomas F.</creatorcontrib><creatorcontrib>Franklin, Paul H.</creatorcontrib><creatorcontrib>Moore, Frank L.</creatorcontrib><title>Guanyl Nucleotides Modulate Binding to Steroid Receptors in Neuronal Membranes</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The recently characterized corticosteroid receptor on amphibian neuronal membranes appears to mediate rapid, stress-induced changes in male reproductive behaviors. Because the transduction mechanisms associated with this receptor are unknown, we performed radioligand binding studies to determine whether this steroid receptor is negatively modulated by guanyl nucleotides. The binding of [3H] corticosterone to neuronal membranes was inhibited by nonhydrolyzable guanyl nucleotides in both equilibrium saturation binding and titration studies. The addition of guanyl nucleotide plus unlabeled corticosterone induced a rapid phase of[3H] corticosterone dissociation from membranes that was not induced by addition of unlabeled ligand alone. Furthermore, the equilibrium binding of [3H] corticosterone and the sensitivity of the receptor to modulation by guanyl nucleotides were both enhanced by Mg2+. These results are consistent with the formation of a ternary complex of steroid, receptor, and guanine nucleotide-binding protein that is subject to regulation by guanyl nucleotides. Therefore, rapid signal transduction through corticosteroid receptors on neuronal membranes appears to be mediated by guanine nucleotide-binding proteins.</description><subject>Agonists</subject><subject>Animals</subject><subject>binding</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Cell Membrane - metabolism</subject><subject>Cellular biology</subject><subject>Corticosteroids</subject><subject>corticosterone</subject><subject>Corticosterone - metabolism</subject><subject>Dithiothreitol - pharmacology</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>guanine nucleotides</subject><subject>Guanine Nucleotides - metabolism</subject><subject>Ligands</subject><subject>Magnesium Chloride - pharmacology</subject><subject>membranes</subject><subject>modulation</subject><subject>Nervous system</subject><subject>neurons</subject><subject>Neurons - metabolism</subject><subject>Nuclear membrane</subject><subject>Nucleotides</subject><subject>P branes</subject><subject>Receptors</subject><subject>Receptors, Glucocorticoid - metabolism</subject><subject>Salamandridae</subject><subject>Signal Transduction</subject><subject>Steroid receptors</subject><subject>Steroids</subject><subject>Taricha granulosa</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9vFCEYhonR1HX16kmTiYfeZvyAYQYOHrTRatKuiT_OhB2-qbNhYQuMsf-9bLbW1YOeIHmfl3wfDyFPKTQUev5y501qpGpUwyWHe2RBQdG6axXcJwsA1teyZe1D8iilDQAoIeGEnFDRAwdYkNX5bPyNq1bz4DDkyWKqLoOdnclYvZm8nfxVlUP1OWMMk60-4YC7HGKqJl-tcI7BG1dd4nYdjcf0mDwYjUv45PZckq_v3n45e19ffDz_cPb6oh6EZLleI6wpSAFouC0T9cioGmk7dOXO5GgsCgMSELlggzW0N12HODJKLSrF-ZK8Ory7m9dbtAP6HI3TuzhtTbzRwUz6z8RP3_RV-K4FE0K2pX9624_hesaU9XZKAzpXlghz0j1TwDvJ_gvSjkErAQr44i9wE-ZYPidpBpT1LS9-lqQ5QEMMKUUc7yamoPc69V6nlkorvddZCs-P9_yNH_wd5fver_S4f_qvXI-zcxl_5AI-O4CbVOzekYwL1QvFfwKl1r0d</recordid><startdate>19920501</startdate><enddate>19920501</enddate><creator>Orchinik, Miles</creator><creator>Murray, Thomas F.</creator><creator>Franklin, Paul H.</creator><creator>Moore, Frank L.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>M7Z</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19920501</creationdate><title>Guanyl Nucleotides Modulate Binding to Steroid Receptors in Neuronal Membranes</title><author>Orchinik, Miles ; Murray, Thomas F. ; Franklin, Paul H. ; Moore, Frank L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c582t-be0b10850ea3d5807e219f14c680728fade5a080ee352cda17a66eef211de9933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Agonists</topic><topic>Animals</topic><topic>binding</topic><topic>Brain</topic><topic>Brain - metabolism</topic><topic>Cell Membrane - metabolism</topic><topic>Cellular biology</topic><topic>Corticosteroids</topic><topic>corticosterone</topic><topic>Corticosterone - metabolism</topic><topic>Dithiothreitol - pharmacology</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>guanine nucleotides</topic><topic>Guanine Nucleotides - metabolism</topic><topic>Ligands</topic><topic>Magnesium Chloride - pharmacology</topic><topic>membranes</topic><topic>modulation</topic><topic>Nervous system</topic><topic>neurons</topic><topic>Neurons - metabolism</topic><topic>Nuclear membrane</topic><topic>Nucleotides</topic><topic>P branes</topic><topic>Receptors</topic><topic>Receptors, Glucocorticoid - metabolism</topic><topic>Salamandridae</topic><topic>Signal Transduction</topic><topic>Steroid receptors</topic><topic>Steroids</topic><topic>Taricha granulosa</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orchinik, Miles</creatorcontrib><creatorcontrib>Murray, Thomas F.</creatorcontrib><creatorcontrib>Franklin, Paul H.</creatorcontrib><creatorcontrib>Moore, Frank L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biochemistry Abstracts 1</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Orchinik, Miles</au><au>Murray, Thomas F.</au><au>Franklin, Paul H.</au><au>Moore, Frank L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Guanyl Nucleotides Modulate Binding to Steroid Receptors in Neuronal Membranes</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1992-05-01</date><risdate>1992</risdate><volume>89</volume><issue>9</issue><spage>3830</spage><epage>3834</epage><pages>3830-3834</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The recently characterized corticosteroid receptor on amphibian neuronal membranes appears to mediate rapid, stress-induced changes in male reproductive behaviors. Because the transduction mechanisms associated with this receptor are unknown, we performed radioligand binding studies to determine whether this steroid receptor is negatively modulated by guanyl nucleotides. The binding of [3H] corticosterone to neuronal membranes was inhibited by nonhydrolyzable guanyl nucleotides in both equilibrium saturation binding and titration studies. The addition of guanyl nucleotide plus unlabeled corticosterone induced a rapid phase of[3H] corticosterone dissociation from membranes that was not induced by addition of unlabeled ligand alone. Furthermore, the equilibrium binding of [3H] corticosterone and the sensitivity of the receptor to modulation by guanyl nucleotides were both enhanced by Mg2+. These results are consistent with the formation of a ternary complex of steroid, receptor, and guanine nucleotide-binding protein that is subject to regulation by guanyl nucleotides. 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| subjects | Agonists Animals binding Brain Brain - metabolism Cell Membrane - metabolism Cellular biology Corticosteroids corticosterone Corticosterone - metabolism Dithiothreitol - pharmacology GTP-Binding Proteins - metabolism guanine nucleotides Guanine Nucleotides - metabolism Ligands Magnesium Chloride - pharmacology membranes modulation Nervous system neurons Neurons - metabolism Nuclear membrane Nucleotides P branes Receptors Receptors, Glucocorticoid - metabolism Salamandridae Signal Transduction Steroid receptors Steroids Taricha granulosa |
| title | Guanyl Nucleotides Modulate Binding to Steroid Receptors in Neuronal Membranes |
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