{"id":"https://openalex.org/W2003117333","doi":"https://doi.org/10.1254/jphs.fp0072230","title":"Contribution of Active and Inactive States of the Human 5-HT4d Receptor to the Functional Activities of 5-HT4\u2013Receptor Agonists","display_name":"Contribution of Active and Inactive States of the Human 5-HT4d Receptor to the Functional Activities of 5-HT4\u2013Receptor Agonists","publication_year":2008,"publication_date":"2008-01-01","ids":{"openalex":"https://openalex.org/W2003117333","doi":"https://doi.org/10.1254/jphs.fp0072230","mag":"2003117333","pmid":"https://pubmed.ncbi.nlm.nih.gov/18587219"},"language":"en","primary_location":{"id":"doi:10.1254/jphs.fp0072230","doi":"https://doi.org/10.1254/jphs.fp0072230","is_oa":true,"landing_page_url":"https://doi.org/10.1254/jphs.fp0072230","pdf_url":"https://www.jstage.jst.go.jp/article/jphs/107/3/107_FP0072230/_pdf","source":{"id":"https://openalex.org/S163931769","display_name":"Journal of Pharmacological Sciences","issn_l":"1347-8613","issn":["1347-8613","1347-8648"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-70"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Pharmacological Sciences","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://www.jstage.jst.go.jp/article/jphs/107/3/107_FP0072230/_pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5111651664","display_name":"Tadayoshi Mikami","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210148786","display_name":"Pfizer (Japan)","ror":"https://ror.org/05pm71w80","country_code":"JP","type":"company","lineage":["https://openalex.org/I180857899","https://openalex.org/I4210148786"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Tadayoshi Mikami","raw_affiliation_strings":["Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan Inc., Taketoyo, Aichi, Japan","Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan Inc., Taketoyo, Aichi, Japan","institution_ids":["https://openalex.org/I4210148786"]},{"raw_affiliation_string":"Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan","institution_ids":["https://openalex.org/I4210148786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108528297","display_name":"Hiromi Sugimoto","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210148786","display_name":"Pfizer (Japan)","ror":"https://ror.org/05pm71w80","country_code":"JP","type":"company","lineage":["https://openalex.org/I180857899","https://openalex.org/I4210148786"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Hiromi Sugimoto","raw_affiliation_strings":["Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan","institution_ids":["https://openalex.org/I4210148786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068762265","display_name":"Rie Naganeo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210148786","display_name":"Pfizer (Japan)","ror":"https://ror.org/05pm71w80","country_code":"JP","type":"company","lineage":["https://openalex.org/I180857899","https://openalex.org/I4210148786"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Rie Naganeo","raw_affiliation_strings":["Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan","institution_ids":["https://openalex.org/I4210148786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113520460","display_name":"Takashi Ohmi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210148786","display_name":"Pfizer (Japan)","ror":"https://ror.org/05pm71w80","country_code":"JP","type":"company","lineage":["https://openalex.org/I180857899","https://openalex.org/I4210148786"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Takashi Ohmi","raw_affiliation_strings":["Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan","institution_ids":["https://openalex.org/I4210148786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108004741","display_name":"Toshiyuki Saito","orcid":"https://orcid.org/0000-0002-3025-1156","observed_orcids":["https://orcid.org/0000-0002-3025-1156"]},"institutions":[{"id":"https://openalex.org/I4210148786","display_name":"Pfizer (Japan)","ror":"https://ror.org/05pm71w80","country_code":"JP","type":"company","lineage":["https://openalex.org/I180857899","https://openalex.org/I4210148786"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Toshiyuki Saito","raw_affiliation_strings":["Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan","institution_ids":["https://openalex.org/I4210148786"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5059906767","display_name":"Hiroyuki Eda","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210148786","display_name":"Pfizer (Japan)","ror":"https://ror.org/05pm71w80","country_code":"JP","type":"company","lineage":["https://openalex.org/I180857899","https://openalex.org/I4210148786"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Hiroyuki Eda","raw_affiliation_strings":["Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan, Inc., Japan","institution_ids":["https://openalex.org/I4210148786"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I4210148786"],"apc_list":{"value":2070,"currency":"USD","value_usd":2070},"apc_paid":null,"fwci":0.448,"has_fulltext":true,"cited_by_count":10,"citation_normalized_percentile":{"value":0.56857276,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":95},"biblio":{"volume":"107","issue":"3","first_page":"251","last_page":"259"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","score":0.9976000189781189,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10056","display_name":"Neurotransmitter Receptor Influence on Behavior","score":0.0008999999845400453,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10077","display_name":"Neuroscience and Neuropharmacology Research","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/5-ht4-receptor","display_name":"5-HT4 receptor","score":0.9760000109672546},{"id":"https://openalex.org/keywords/receptor-agonists","display_name":"receptor agonists","score":0.5979999899864197},{"id":"https://openalex.org/keywords/binding-affinity","display_name":"binding affinity","score":0.7149999737739563},{"id":"https://openalex.org/keywords/gr113808","display_name":"GR113808","score":0.8019999861717224},{"id":"https://openalex.org/keywords/serotonin","display_name":"serotonin","score":0.7630000114440918},{"id":"https://openalex.org/keywords/gtpgammas","display_name":"GTP gamma S","score":0.7900000214576721},{"id":"https://openalex.org/keywords/partial-agonists","display_name":"partial agonists","score":0.675000011920929},{"id":"https://openalex.org/keywords/full-agonists","display_name":"full agonists","score":0.9359999895095825},{"id":"https://openalex.org/keywords/tegaserod","display_name":"tegaserod","score":0.8389999866485596},{"id":"https://openalex.org/keywords/5-methoxytryptamine","display_name":"5-methoxytryptamine","score":0.9829999804496765},{"id":"https://openalex.org/keywords/receptor-binding-sites","display_name":"receptor binding sites","score":0.5090000033378601},{"id":"https://openalex.org/keywords/competitive-binding","display_name":"competitive binding","score":0.6489999890327454}],"concepts":[{"id":"https://openalex.org/C2780283098","wikidata":"https://www.wikidata.org/wiki/Q4688960","display_name":"Affinities","level":2,"score":0.7481068968772888},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6740200519561768},{"id":"https://openalex.org/C2778938600","wikidata":"https://www.wikidata.org/wiki/Q389934","display_name":"Agonist","level":3,"score":0.6416710615158081},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.6349023580551147},{"id":"https://openalex.org/C3018795828","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Binding affinities","level":3,"score":0.6326177716255188},{"id":"https://openalex.org/C2778684643","wikidata":"https://www.wikidata.org/wiki/Q5514740","display_name":"GTPgammaS","level":4,"score":0.631244957447052},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.5894138216972351},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.5500850677490234},{"id":"https://openalex.org/C2777995097","wikidata":"https://www.wikidata.org/wiki/Q422462","display_name":"Guanosine","level":2,"score":0.5001075267791748},{"id":"https://openalex.org/C53910766","wikidata":"https://www.wikidata.org/wiki/Q238516","display_name":"5-HT receptor","level":4,"score":0.4735645055770874},{"id":"https://openalex.org/C2909005528","wikidata":"https://www.wikidata.org/wiki/Q626478","display_name":"Radioligand Assay","level":3,"score":0.44247934222221375},{"id":"https://openalex.org/C58732023","wikidata":"https://www.wikidata.org/wiki/Q770260","display_name":"Partial agonist","level":4,"score":0.41352295875549316},{"id":"https://openalex.org/C2775864247","wikidata":"https://www.wikidata.org/wiki/Q167934","display_name":"Serotonin","level":3,"score":0.25159314274787903},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2326892912387848}],"mesh":[{"descriptor_ui":"D004305","descriptor_name":"Dose-Response Relationship, Drug","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007211","descriptor_name":"Indoles","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D012701","descriptor_name":"Serotonin","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D013449","descriptor_name":"Sulfonamides","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D016244","descriptor_name":"Guanosine 5'-O-(3-Thiotriphosphate)","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D017366","descriptor_name":"Serotonin Receptor Agonists","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D058825","descriptor_name":"Serotonin 5-HT1 Receptor Agonists","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D058828","descriptor_name":"Serotonin 5-HT4 Receptor Agonists","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1254/jphs.fp0072230","doi":"https://doi.org/10.1254/jphs.fp0072230","is_oa":true,"landing_page_url":"https://doi.org/10.1254/jphs.fp0072230","pdf_url":"https://www.jstage.jst.go.jp/article/jphs/107/3/107_FP0072230/_pdf","source":{"id":"https://openalex.org/S163931769","display_name":"Journal of Pharmacological Sciences","issn_l":"1347-8613","issn":["1347-8613","1347-8648"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-70"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Pharmacological Sciences","raw_type":"journal-article"},{"id":"pmid:18587219","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/18587219","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of pharmacological sciences","raw_type":"Journal Article"},{"id":"pmh:oai:doaj.org/article:b2a6c2c6d7794e359134aa35f41695d7","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/b2a6c2c6d7794e359134aa35f41695d7","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Journal of Pharmacological Sciences, Vol 107, Iss 3, Pp 251-259 (2008)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.1254/jphs.fp0072230","doi":"https://doi.org/10.1254/jphs.fp0072230","is_oa":true,"landing_page_url":"https://doi.org/10.1254/jphs.fp0072230","pdf_url":"https://www.jstage.jst.go.jp/article/jphs/107/3/107_FP0072230/_pdf","source":{"id":"https://openalex.org/S163931769","display_name":"Journal of Pharmacological Sciences","issn_l":"1347-8613","issn":["1347-8613","1347-8648"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-70"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Pharmacological Sciences","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.5683000087738037}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2003117333.pdf","grobid_xml":"https://content.openalex.org/works/W2003117333.grobid-xml"},"referenced_works_count":27,"referenced_works":["https://openalex.org/W52436622","https://openalex.org/W67730575","https://openalex.org/W1481686455","https://openalex.org/W1906396765","https://openalex.org/W1965835906","https://openalex.org/W1965961744","https://openalex.org/W1972923838","https://openalex.org/W1997018720","https://openalex.org/W1997670741","https://openalex.org/W2014106658","https://openalex.org/W2033579865","https://openalex.org/W2033603525","https://openalex.org/W2042745003","https://openalex.org/W2043972017","https://openalex.org/W2053188024","https://openalex.org/W2072827946","https://openalex.org/W2076811819","https://openalex.org/W2078831015","https://openalex.org/W2080086356","https://openalex.org/W2094580786","https://openalex.org/W2095775529","https://openalex.org/W2127792081","https://openalex.org/W2131713441","https://openalex.org/W2139129258","https://openalex.org/W2163255052","https://openalex.org/W2169437499","https://openalex.org/W2333358414"],"related_works":["https://openalex.org/W2078831015","https://openalex.org/W2024964650","https://openalex.org/W2053074524","https://openalex.org/W1997018720","https://openalex.org/W2088058665","https://openalex.org/W2085547042","https://openalex.org/W2041032137","https://openalex.org/W2060598688","https://openalex.org/W2072399553","https://openalex.org/W2163255052"],"abstract_inverted_index":{"In":[0,91],"the":[1,11,18,22,30,53,69,77,83,148,156,162,172,178],"present":[2],"study,":[3],"binding":[4,35,39,59,66,73,93,110,115,125,129,136,180],"affinities":[5,107,122,137,173],"of":[6,71,79,85,155,165,174],"5-hydroxytryptamine-4":[7],"(5-HT(4))":[8],"ligands":[9,176],"for":[10,108,113,123,127,138],"human":[12,54,157],"5-HT(4d)":[13,55,158],"receptor":[14,56,159],"were":[15],"determined":[16],"using":[17,49],"agonist":[19],"[(3)H]5-HT":[20,34,50,72,109,124],"and":[21,37,100,152,168],"selective":[23],"5-HT(4)":[24,45,166,175],"antagonist":[25],"[(3)H]GR113,808.":[26],"We":[27],"also":[28],"compared":[29],"affinity":[31],"differences":[32],"between":[33,150],"(K(H))":[36,111],"[(3)H]GR113,808":[38,62,86,114,128],"(K(L))":[40,116],"with":[41],"their":[42],"activities":[43,164],"as":[44,98],"ligands.":[46],"Binding":[47],"studies":[48],"revealed":[51],"that":[52,147],"has":[57],"two":[58],"sites,":[60],"whereas":[61],"yielded":[63],"a":[64],"single":[65],"site.":[67],"Additionally,":[68],"number":[70,84],"sites":[74,87],"decreased":[75],"in":[76,177],"presence":[78],"guanosine-5'-O-(3-thiotriphosphate)":[80],"(GTPgammaS),":[81],"but":[82],"did":[88],"not":[89],"change.":[90],"competitive":[92,179],"assays,":[94],"full":[95],"agonists":[96,133],"such":[97],"5-methoxytryptamine":[99],"tegaserod":[101],"showed":[102,120],"2-":[103],"to":[104],"8-fold":[105],"higher":[106],"than":[112,126],"(K(H)<K(L)).":[117],"Conversely,":[118],"antagonists":[119],"lower":[121],"(K(H)>K(L)).":[130],"Finally,":[131],"partial":[132],"displayed":[134],"similar":[135],"both":[139],"radioligands":[140],"(K(H)":[141],"=":[142],"K(L)).":[143],"These":[144],"findings":[145],"suggest":[146],"equilibrium":[149],"active":[151],"inactive":[153],"states":[154,170],"relies":[160],"on":[161],"functional":[163],"ligands,":[167],"these":[169],"affect":[171],"assay.":[181]},"counts_by_year":[{"year":2023,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2017,"cited_by_count":1},{"year":2013,"cited_by_count":1},{"year":2012,"cited_by_count":2}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}