Taking The Time To Study Competitive Antagonism
Selective receptor antagonists are one of the most powerful resources in a pharmacologist's toolkit and are essential for the identification and classification of receptor subtypes and dissecting their roles in normal and abnormal body function. However, when the actions of antagonists are meas...
Gespeichert in:
| Veröffentlicht in: | British journal of pharmacology 2007-03, Vol.150 (5), p.541-551 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 551 |
|---|---|
| container_issue | 5 |
| container_start_page | 541 |
| container_title | British journal of pharmacology |
| container_volume | 150 |
| creator | Wyllie, D J A Chen, P E |
| description | Selective receptor antagonists are one of the most powerful resources in a pharmacologist's toolkit and are essential for the identification and classification of receptor subtypes and dissecting their roles in normal and abnormal body function. However, when the actions of antagonists are measured inappropriately and misleading results are reported, confusion and wrong interpretations ensue. This article gives a general overview of Schild analysis and the method of determining antagonist equilibrium constants. We demonstrate why this technique is preferable in the study of competitive receptor antagonism than the calculation of antagonist concentration that inhibit agonist‐evoked responses by 50%. In addition we show how the use of Schild analysis can provide information on the outcome of single amino acid mutations in structure‐function studies of receptors. Finally, we illustrate the need for caution when studying the effects of potent antagonists on synaptic transmission where the timescale of events under investigation is such that ligands and receptors never reach steady‐state occupancy.
British Journal of Pharmacology (2007) 150, 541–551. doi:10.1038/sj.bjp.0706997 |
| doi_str_mv | 10.1038/sj.bjp.0706997 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2189774</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1227126161</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4889-ceab328592df6d072fcaf62705def76e2041b504fa726c17359043b2538287b83</originalsourceid><addsrcrecordid>eNqFkEtLw0AUhQdRbK1uXUoQXCadRyZ3shFqUSsUFKzrYZJM2ol51Exa6b93tMHHys29i_vdcw4HoXOCA4KZGNsiSIp1gAFHcQwHaEhCiHzOBDlEQ4wx-IQIMUAn1hYYuyPwYzQgQEPOgAzReKFeTb30FivtLUzlRuM9d5ts502baq0705mt9iZ1p5ZNbWx1io5yVVp91u8Rerm7XUxn_vzx_mE6mftpKETsp1oljAoe0yyPMgw0T1UeUcA80zlEmuKQJByHuQIapQQYj3HIEuqCUwGJYCN0vdddb5JKZ6muu1aVct2aSrU72Sgj_15qs5LLZispETFA6AQue4G2edto28mi2bS1y-wQIDEHzh0U7KG0baxtdf5tQLD87FfaQrp-Zd-ve7j4HesH7wt1wFUPKJuqMm9VnRr7w4mIsehLiO65d1Pq3T-28uZpxkjMPgAe55Lm</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>217195755</pqid></control><display><type>article</type><title>Taking The Time To Study Competitive Antagonism</title><source>MEDLINE</source><source>Wiley Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Free Content</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Wyllie, D J A ; Chen, P E</creator><creatorcontrib>Wyllie, D J A ; Chen, P E</creatorcontrib><description>Selective receptor antagonists are one of the most powerful resources in a pharmacologist's toolkit and are essential for the identification and classification of receptor subtypes and dissecting their roles in normal and abnormal body function. However, when the actions of antagonists are measured inappropriately and misleading results are reported, confusion and wrong interpretations ensue. This article gives a general overview of Schild analysis and the method of determining antagonist equilibrium constants. We demonstrate why this technique is preferable in the study of competitive receptor antagonism than the calculation of antagonist concentration that inhibit agonist‐evoked responses by 50%. In addition we show how the use of Schild analysis can provide information on the outcome of single amino acid mutations in structure‐function studies of receptors. Finally, we illustrate the need for caution when studying the effects of potent antagonists on synaptic transmission where the timescale of events under investigation is such that ligands and receptors never reach steady‐state occupancy.
British Journal of Pharmacology (2007) 150, 541–551. doi:10.1038/sj.bjp.0706997</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0706997</identifier><identifier>PMID: 17245371</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>agonist ; Animals ; antagonist ; binding ; Binding, Competitive ; Biological and medical sciences ; Computer Simulation ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical - methods ; D‐AP5 ; equilibrium constant ; Excitatory Amino Acid Agonists - metabolism ; Excitatory Amino Acid Agonists - pharmacology ; Excitatory Amino Acid Antagonists - metabolism ; Excitatory Amino Acid Antagonists - pharmacology ; gating ; Humans ; inhibition ; Ion Channel Gating - drug effects ; Ion Channels - agonists ; Ion Channels - antagonists & inhibitors ; Ion Channels - genetics ; Ion Channels - metabolism ; Kinetics ; Ligands ; Medical sciences ; Models, Biological ; Nicotinic Agonists - metabolism ; Nicotinic Agonists - pharmacology ; Nicotinic Antagonists - metabolism ; Nicotinic Antagonists - pharmacology ; NVP‐AAM077 ; Pharmacology. Drug treatments ; Point Mutation ; Protein Binding ; Receptors, Cell Surface - agonists ; Receptors, Cell Surface - antagonists & inhibitors ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - metabolism ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Receptors, Nicotinic - drug effects ; Reproducibility of Results ; Reviews ; Schild analysis ; Synaptic Transmission - drug effects</subject><ispartof>British journal of pharmacology, 2007-03, Vol.150 (5), p.541-551</ispartof><rights>2007 British Pharmacological Society</rights><rights>2007 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Mar 2007</rights><rights>Copyright 2007, Nature Publishing Group 2007 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4889-ceab328592df6d072fcaf62705def76e2041b504fa726c17359043b2538287b83</citedby><cites>FETCH-LOGICAL-c4889-ceab328592df6d072fcaf62705def76e2041b504fa726c17359043b2538287b83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189774/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189774/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18633697$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17245371$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wyllie, D J A</creatorcontrib><creatorcontrib>Chen, P E</creatorcontrib><title>Taking The Time To Study Competitive Antagonism</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Selective receptor antagonists are one of the most powerful resources in a pharmacologist's toolkit and are essential for the identification and classification of receptor subtypes and dissecting their roles in normal and abnormal body function. However, when the actions of antagonists are measured inappropriately and misleading results are reported, confusion and wrong interpretations ensue. This article gives a general overview of Schild analysis and the method of determining antagonist equilibrium constants. We demonstrate why this technique is preferable in the study of competitive receptor antagonism than the calculation of antagonist concentration that inhibit agonist‐evoked responses by 50%. In addition we show how the use of Schild analysis can provide information on the outcome of single amino acid mutations in structure‐function studies of receptors. Finally, we illustrate the need for caution when studying the effects of potent antagonists on synaptic transmission where the timescale of events under investigation is such that ligands and receptors never reach steady‐state occupancy.
British Journal of Pharmacology (2007) 150, 541–551. doi:10.1038/sj.bjp.0706997</description><subject>agonist</subject><subject>Animals</subject><subject>antagonist</subject><subject>binding</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Computer Simulation</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>D‐AP5</subject><subject>equilibrium constant</subject><subject>Excitatory Amino Acid Agonists - metabolism</subject><subject>Excitatory Amino Acid Agonists - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - metabolism</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>gating</subject><subject>Humans</subject><subject>inhibition</subject><subject>Ion Channel Gating - drug effects</subject><subject>Ion Channels - agonists</subject><subject>Ion Channels - antagonists & inhibitors</subject><subject>Ion Channels - genetics</subject><subject>Ion Channels - metabolism</subject><subject>Kinetics</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Models, Biological</subject><subject>Nicotinic Agonists - metabolism</subject><subject>Nicotinic Agonists - pharmacology</subject><subject>Nicotinic Antagonists - metabolism</subject><subject>Nicotinic Antagonists - pharmacology</subject><subject>NVP‐AAM077</subject><subject>Pharmacology. Drug treatments</subject><subject>Point Mutation</subject><subject>Protein Binding</subject><subject>Receptors, Cell Surface - agonists</subject><subject>Receptors, Cell Surface - antagonists & inhibitors</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Receptors, Nicotinic - drug effects</subject><subject>Reproducibility of Results</subject><subject>Reviews</subject><subject>Schild analysis</subject><subject>Synaptic Transmission - drug effects</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkEtLw0AUhQdRbK1uXUoQXCadRyZ3shFqUSsUFKzrYZJM2ol51Exa6b93tMHHys29i_vdcw4HoXOCA4KZGNsiSIp1gAFHcQwHaEhCiHzOBDlEQ4wx-IQIMUAn1hYYuyPwYzQgQEPOgAzReKFeTb30FivtLUzlRuM9d5ts502baq0705mt9iZ1p5ZNbWx1io5yVVp91u8Rerm7XUxn_vzx_mE6mftpKETsp1oljAoe0yyPMgw0T1UeUcA80zlEmuKQJByHuQIapQQYj3HIEuqCUwGJYCN0vdddb5JKZ6muu1aVct2aSrU72Sgj_15qs5LLZispETFA6AQue4G2edto28mi2bS1y-wQIDEHzh0U7KG0baxtdf5tQLD87FfaQrp-Zd-ve7j4HesH7wt1wFUPKJuqMm9VnRr7w4mIsehLiO65d1Pq3T-28uZpxkjMPgAe55Lm</recordid><startdate>200703</startdate><enddate>200703</enddate><creator>Wyllie, D J A</creator><creator>Chen, P E</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</general><general>Nature Publishing Group</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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>200703</creationdate><title>Taking The Time To Study Competitive Antagonism</title><author>Wyllie, D J A ; Chen, P E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4889-ceab328592df6d072fcaf62705def76e2041b504fa726c17359043b2538287b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>agonist</topic><topic>Animals</topic><topic>antagonist</topic><topic>binding</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Computer Simulation</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>D‐AP5</topic><topic>equilibrium constant</topic><topic>Excitatory Amino Acid Agonists - metabolism</topic><topic>Excitatory Amino Acid Agonists - pharmacology</topic><topic>Excitatory Amino Acid Antagonists - metabolism</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>gating</topic><topic>Humans</topic><topic>inhibition</topic><topic>Ion Channel Gating - drug effects</topic><topic>Ion Channels - agonists</topic><topic>Ion Channels - antagonists & inhibitors</topic><topic>Ion Channels - genetics</topic><topic>Ion Channels - metabolism</topic><topic>Kinetics</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Models, Biological</topic><topic>Nicotinic Agonists - metabolism</topic><topic>Nicotinic Agonists - pharmacology</topic><topic>Nicotinic Antagonists - metabolism</topic><topic>Nicotinic Antagonists - pharmacology</topic><topic>NVP‐AAM077</topic><topic>Pharmacology. Drug treatments</topic><topic>Point Mutation</topic><topic>Protein Binding</topic><topic>Receptors, Cell Surface - agonists</topic><topic>Receptors, Cell Surface - antagonists & inhibitors</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Receptors, Nicotinic - drug effects</topic><topic>Reproducibility of Results</topic><topic>Reviews</topic><topic>Schild analysis</topic><topic>Synaptic Transmission - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wyllie, D J A</creatorcontrib><creatorcontrib>Chen, P E</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wyllie, D J A</au><au>Chen, P E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Taking The Time To Study Competitive Antagonism</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2007-03</date><risdate>2007</risdate><volume>150</volume><issue>5</issue><spage>541</spage><epage>551</epage><pages>541-551</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>Selective receptor antagonists are one of the most powerful resources in a pharmacologist's toolkit and are essential for the identification and classification of receptor subtypes and dissecting their roles in normal and abnormal body function. However, when the actions of antagonists are measured inappropriately and misleading results are reported, confusion and wrong interpretations ensue. This article gives a general overview of Schild analysis and the method of determining antagonist equilibrium constants. We demonstrate why this technique is preferable in the study of competitive receptor antagonism than the calculation of antagonist concentration that inhibit agonist‐evoked responses by 50%. In addition we show how the use of Schild analysis can provide information on the outcome of single amino acid mutations in structure‐function studies of receptors. Finally, we illustrate the need for caution when studying the effects of potent antagonists on synaptic transmission where the timescale of events under investigation is such that ligands and receptors never reach steady‐state occupancy.
British Journal of Pharmacology (2007) 150, 541–551. doi:10.1038/sj.bjp.0706997</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>17245371</pmid><doi>10.1038/sj.bjp.0706997</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-1188 |
| ispartof | British journal of pharmacology, 2007-03, Vol.150 (5), p.541-551 |
| issn | 0007-1188 1476-5381 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2189774 |
| source | MEDLINE; Wiley Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Free Content; PubMed Central; Alma/SFX Local Collection |
| subjects | agonist Animals antagonist binding Binding, Competitive Biological and medical sciences Computer Simulation Dose-Response Relationship, Drug Drug Evaluation, Preclinical - methods D‐AP5 equilibrium constant Excitatory Amino Acid Agonists - metabolism Excitatory Amino Acid Agonists - pharmacology Excitatory Amino Acid Antagonists - metabolism Excitatory Amino Acid Antagonists - pharmacology gating Humans inhibition Ion Channel Gating - drug effects Ion Channels - agonists Ion Channels - antagonists & inhibitors Ion Channels - genetics Ion Channels - metabolism Kinetics Ligands Medical sciences Models, Biological Nicotinic Agonists - metabolism Nicotinic Agonists - pharmacology Nicotinic Antagonists - metabolism Nicotinic Antagonists - pharmacology NVP‐AAM077 Pharmacology. Drug treatments Point Mutation Protein Binding Receptors, Cell Surface - agonists Receptors, Cell Surface - antagonists & inhibitors Receptors, Cell Surface - genetics Receptors, Cell Surface - metabolism Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, Nicotinic - drug effects Reproducibility of Results Reviews Schild analysis Synaptic Transmission - drug effects |
| title | Taking The Time To Study Competitive Antagonism |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T19%3A29%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Taking%20The%20Time%20To%20Study%20Competitive%20Antagonism&rft.jtitle=British%20journal%20of%20pharmacology&rft.au=Wyllie,%20D%20J%20A&rft.date=2007-03&rft.volume=150&rft.issue=5&rft.spage=541&rft.epage=551&rft.pages=541-551&rft.issn=0007-1188&rft.eissn=1476-5381&rft.coden=BJPCBM&rft_id=info:doi/10.1038/sj.bjp.0706997&rft_dat=%3Cproquest_pubme%3E1227126161%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=217195755&rft_id=info:pmid/17245371&rfr_iscdi=true |