Loading…
Distinct functions of the two isoforms of dopamine D2 receptors
Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse 1 , 2 , 3 , 4 , 5 , 6 , 7 . D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia 8 . By a me...
Saved in:
| Published in: | Nature (London) 2000-11, Vol.408 (6809), p.199-203 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c6202-421c1c5ae6176af4b54ac06bebcb2baebf39e798b82fc970dbd1f167a2afe28b3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c6202-421c1c5ae6176af4b54ac06bebcb2baebf39e798b82fc970dbd1f167a2afe28b3 |
| container_end_page | 203 |
| container_issue | 6809 |
| container_start_page | 199 |
| container_title | Nature (London) |
| container_volume | 408 |
| creator | Usiello, Alessandro Baik, Ja-Hyun Rougé-Pont, Françoise Picetti, Roberto Dierich, Andrée LeMeur, Marianne Piazza, Pier Vincenzo Borrelli, Emiliana |
| description | Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse
1
,
2
,
3
,
4
,
5
,
6
,
7
. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia
8
. By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms
9
, D2S and D2L, previously thought to have the same function. Here we show that these receptors have distinct functions
in vivo
; D2L acts mainly at postsynaptic sites and D2S serves presynaptic autoreceptor functions. The cataleptic effects of the widely used antipsychotic haloperidol
1
are absent in D2L-deficient mice. This suggests that D2L is targeted by haloperidol, with implications for treatment of neuropsychiatric disorders. The absence of D2L reveals that D2S inhibits D1 receptor-mediated functions, uncovering a circuit of signalling interference between dopamine receptors. |
| doi_str_mv | 10.1038/35041572 |
| format | article |
| fullrecord | <record><control><sourceid>gale_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_04094316v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A218529969</galeid><sourcerecordid>A218529969</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6202-421c1c5ae6176af4b54ac06bebcb2baebf39e798b82fc970dbd1f167a2afe28b3</originalsourceid><addsrcrecordid>eNp90u1r1DAYAPAiijun4F8gRUEd0pm3JuknOW7qBoeCTvwY0tyTW0bbdEm76X9vzjvvPJ0SSODJL0_enix7jNExRlS-piViuBTkTjbBTPCCcSnuZhOEiCyQpPwgexDjJUKoxILdzw4wRrKqBJ1kb05cHFxnhtyOqXe-i7m3-XAB-XDjcxe99aH9GVv4Xreug_yE5AEM9IMP8WF2z-omwqPNeJh9eff2fHZazD--P5tN54XhBJGCEWywKTVwLLi2rC6ZNojXUJua1BpqSysQlawlsaYSaFEvsMVcaKItEFnTw-xonfdCN6oPrtXhu_LaqdPpXK1iiKGKUcyvcbIv1rYP_mqEOKjWRQNNozvwY1QiOUklF0k-_69Mh6Ulq8oEn_4BL_0YunRjRRBjgjKx2rdYo6VuQLnO-iFos4QOgm58B9al8JRgWZKq4tUu6Z43vbtSv6PjW1BqC2iduTXr0d6CZAb4Niz1GKM6-_xp3776t52ef5192Ncv19oEH2MAu_0IjNSqDtWvOkz0yea9xrqFxQ5uCi-BZxugo9GNDbozLm6dRJSkb9reJaaJbglh9-x_bfkDJzbqsg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>204473471</pqid></control><display><type>article</type><title>Distinct functions of the two isoforms of dopamine D2 receptors</title><source>Nature</source><creator>Usiello, Alessandro ; Baik, Ja-Hyun ; Rougé-Pont, Françoise ; Picetti, Roberto ; Dierich, Andrée ; LeMeur, Marianne ; Piazza, Pier Vincenzo ; Borrelli, Emiliana</creator><creatorcontrib>Usiello, Alessandro ; Baik, Ja-Hyun ; Rougé-Pont, Françoise ; Picetti, Roberto ; Dierich, Andrée ; LeMeur, Marianne ; Piazza, Pier Vincenzo ; Borrelli, Emiliana</creatorcontrib><description>Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse
1
,
2
,
3
,
4
,
5
,
6
,
7
. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia
8
. By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms
9
, D2S and D2L, previously thought to have the same function. Here we show that these receptors have distinct functions
in vivo
; D2L acts mainly at postsynaptic sites and D2S serves presynaptic autoreceptor functions. The cataleptic effects of the widely used antipsychotic haloperidol
1
are absent in D2L-deficient mice. This suggests that D2L is targeted by haloperidol, with implications for treatment of neuropsychiatric disorders. The absence of D2L reveals that D2S inhibits D1 receptor-mediated functions, uncovering a circuit of signalling interference between dopamine receptors.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/35041572</identifier><identifier>PMID: 11089973</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Apomorphine - pharmacology ; Benzazepines - pharmacology ; Biological and medical sciences ; Catalepsy - metabolism ; Cell receptors ; Cell structures and functions ; Cellular signal transduction ; Chimera ; Dopamine - metabolism ; Dopamine Agonists - pharmacology ; Dopamine Antagonists - pharmacology ; Dopamine receptors ; Drug abuse ; Drug therapy ; Drugs ; Fundamental and applied biological sciences. Psychology ; Genetic aspects ; Genetics ; Haloperidol - pharmacology ; Humanities and Social Sciences ; letter ; Life Sciences ; Mental disorders ; Mental illness ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular and cellular biology ; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine) ; multidisciplinary ; Mutagenesis ; Neurology ; Physiological aspects ; Postsynaptic potentials ; Protein Isoforms - chemistry ; Protein Isoforms - physiology ; Quinpirole - pharmacology ; Receptors, Dopamine D2 - chemistry ; Receptors, Dopamine D2 - genetics ; Receptors, Dopamine D2 - physiology ; Science ; Science (multidisciplinary) ; Signal Transduction ; Spiperone - pharmacology ; Synapses - physiology</subject><ispartof>Nature (London), 2000-11, Vol.408 (6809), p.199-203</ispartof><rights>Macmillan Magazines Ltd. 2000</rights><rights>2001 INIST-CNRS</rights><rights>COPYRIGHT 2000 Nature Publishing Group</rights><rights>Copyright Macmillan Journals Ltd. Nov 9, 2000</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6202-421c1c5ae6176af4b54ac06bebcb2baebf39e798b82fc970dbd1f167a2afe28b3</citedby><cites>FETCH-LOGICAL-c6202-421c1c5ae6176af4b54ac06bebcb2baebf39e798b82fc970dbd1f167a2afe28b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=803274$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11089973$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04094316$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Usiello, Alessandro</creatorcontrib><creatorcontrib>Baik, Ja-Hyun</creatorcontrib><creatorcontrib>Rougé-Pont, Françoise</creatorcontrib><creatorcontrib>Picetti, Roberto</creatorcontrib><creatorcontrib>Dierich, Andrée</creatorcontrib><creatorcontrib>LeMeur, Marianne</creatorcontrib><creatorcontrib>Piazza, Pier Vincenzo</creatorcontrib><creatorcontrib>Borrelli, Emiliana</creatorcontrib><title>Distinct functions of the two isoforms of dopamine D2 receptors</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse
1
,
2
,
3
,
4
,
5
,
6
,
7
. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia
8
. By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms
9
, D2S and D2L, previously thought to have the same function. Here we show that these receptors have distinct functions
in vivo
; D2L acts mainly at postsynaptic sites and D2S serves presynaptic autoreceptor functions. The cataleptic effects of the widely used antipsychotic haloperidol
1
are absent in D2L-deficient mice. This suggests that D2L is targeted by haloperidol, with implications for treatment of neuropsychiatric disorders. The absence of D2L reveals that D2S inhibits D1 receptor-mediated functions, uncovering a circuit of signalling interference between dopamine receptors.</description><subject>Animals</subject><subject>Apomorphine - pharmacology</subject><subject>Benzazepines - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Catalepsy - metabolism</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>Cellular signal transduction</subject><subject>Chimera</subject><subject>Dopamine - metabolism</subject><subject>Dopamine Agonists - pharmacology</subject><subject>Dopamine Antagonists - pharmacology</subject><subject>Dopamine receptors</subject><subject>Drug abuse</subject><subject>Drug therapy</subject><subject>Drugs</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Haloperidol - pharmacology</subject><subject>Humanities and Social Sciences</subject><subject>letter</subject><subject>Life Sciences</subject><subject>Mental disorders</subject><subject>Mental illness</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Molecular and cellular biology</subject><subject>Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine)</subject><subject>multidisciplinary</subject><subject>Mutagenesis</subject><subject>Neurology</subject><subject>Physiological aspects</subject><subject>Postsynaptic potentials</subject><subject>Protein Isoforms - chemistry</subject><subject>Protein Isoforms - physiology</subject><subject>Quinpirole - pharmacology</subject><subject>Receptors, Dopamine D2 - chemistry</subject><subject>Receptors, Dopamine D2 - genetics</subject><subject>Receptors, Dopamine D2 - physiology</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal Transduction</subject><subject>Spiperone - pharmacology</subject><subject>Synapses - physiology</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><recordid>eNp90u1r1DAYAPAiijun4F8gRUEd0pm3JuknOW7qBoeCTvwY0tyTW0bbdEm76X9vzjvvPJ0SSODJL0_enix7jNExRlS-piViuBTkTjbBTPCCcSnuZhOEiCyQpPwgexDjJUKoxILdzw4wRrKqBJ1kb05cHFxnhtyOqXe-i7m3-XAB-XDjcxe99aH9GVv4Xreug_yE5AEM9IMP8WF2z-omwqPNeJh9eff2fHZazD--P5tN54XhBJGCEWywKTVwLLi2rC6ZNojXUJua1BpqSysQlawlsaYSaFEvsMVcaKItEFnTw-xonfdCN6oPrtXhu_LaqdPpXK1iiKGKUcyvcbIv1rYP_mqEOKjWRQNNozvwY1QiOUklF0k-_69Mh6Ulq8oEn_4BL_0YunRjRRBjgjKx2rdYo6VuQLnO-iFos4QOgm58B9al8JRgWZKq4tUu6Z43vbtSv6PjW1BqC2iduTXr0d6CZAb4Niz1GKM6-_xp3776t52ef5192Ncv19oEH2MAu_0IjNSqDtWvOkz0yea9xrqFxQ5uCi-BZxugo9GNDbozLm6dRJSkb9reJaaJbglh9-x_bfkDJzbqsg</recordid><startdate>20001109</startdate><enddate>20001109</enddate><creator>Usiello, Alessandro</creator><creator>Baik, Ja-Hyun</creator><creator>Rougé-Pont, Françoise</creator><creator>Picetti, Roberto</creator><creator>Dierich, Andrée</creator><creator>LeMeur, Marianne</creator><creator>Piazza, Pier Vincenzo</creator><creator>Borrelli, Emiliana</creator><general>Nature Publishing Group UK</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>ATWCN</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7SC</scope><scope>7SP</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>1XC</scope></search><sort><creationdate>20001109</creationdate><title>Distinct functions of the two isoforms of dopamine D2 receptors</title><author>Usiello, Alessandro ; Baik, Ja-Hyun ; Rougé-Pont, Françoise ; Picetti, Roberto ; Dierich, Andrée ; LeMeur, Marianne ; Piazza, Pier Vincenzo ; Borrelli, Emiliana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6202-421c1c5ae6176af4b54ac06bebcb2baebf39e798b82fc970dbd1f167a2afe28b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Apomorphine - pharmacology</topic><topic>Benzazepines - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Catalepsy - metabolism</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>Cellular signal transduction</topic><topic>Chimera</topic><topic>Dopamine - metabolism</topic><topic>Dopamine Agonists - pharmacology</topic><topic>Dopamine Antagonists - pharmacology</topic><topic>Dopamine receptors</topic><topic>Drug abuse</topic><topic>Drug therapy</topic><topic>Drugs</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic aspects</topic><topic>Genetics</topic><topic>Haloperidol - pharmacology</topic><topic>Humanities and Social Sciences</topic><topic>letter</topic><topic>Life Sciences</topic><topic>Mental disorders</topic><topic>Mental illness</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Molecular and cellular biology</topic><topic>Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine)</topic><topic>multidisciplinary</topic><topic>Mutagenesis</topic><topic>Neurology</topic><topic>Physiological aspects</topic><topic>Postsynaptic potentials</topic><topic>Protein Isoforms - chemistry</topic><topic>Protein Isoforms - physiology</topic><topic>Quinpirole - pharmacology</topic><topic>Receptors, Dopamine D2 - chemistry</topic><topic>Receptors, Dopamine D2 - genetics</topic><topic>Receptors, Dopamine D2 - physiology</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal Transduction</topic><topic>Spiperone - pharmacology</topic><topic>Synapses - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Usiello, Alessandro</creatorcontrib><creatorcontrib>Baik, Ja-Hyun</creatorcontrib><creatorcontrib>Rougé-Pont, Françoise</creatorcontrib><creatorcontrib>Picetti, Roberto</creatorcontrib><creatorcontrib>Dierich, Andrée</creatorcontrib><creatorcontrib>LeMeur, Marianne</creatorcontrib><creatorcontrib>Piazza, Pier Vincenzo</creatorcontrib><creatorcontrib>Borrelli, Emiliana</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>Gale In Context: Middle School</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical 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>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials science collection</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 One Psychology</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>SIRS Editorial</collection><collection>Environment Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Usiello, Alessandro</au><au>Baik, Ja-Hyun</au><au>Rougé-Pont, Françoise</au><au>Picetti, Roberto</au><au>Dierich, Andrée</au><au>LeMeur, Marianne</au><au>Piazza, Pier Vincenzo</au><au>Borrelli, Emiliana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinct functions of the two isoforms of dopamine D2 receptors</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2000-11-09</date><risdate>2000</risdate><volume>408</volume><issue>6809</issue><spage>199</spage><epage>203</epage><pages>199-203</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse
1
,
2
,
3
,
4
,
5
,
6
,
7
. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia
8
. By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms
9
, D2S and D2L, previously thought to have the same function. Here we show that these receptors have distinct functions
in vivo
; D2L acts mainly at postsynaptic sites and D2S serves presynaptic autoreceptor functions. The cataleptic effects of the widely used antipsychotic haloperidol
1
are absent in D2L-deficient mice. This suggests that D2L is targeted by haloperidol, with implications for treatment of neuropsychiatric disorders. The absence of D2L reveals that D2S inhibits D1 receptor-mediated functions, uncovering a circuit of signalling interference between dopamine receptors.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>11089973</pmid><doi>10.1038/35041572</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 2000-11, Vol.408 (6809), p.199-203 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_04094316v1 |
| source | Nature |
| subjects | Animals Apomorphine - pharmacology Benzazepines - pharmacology Biological and medical sciences Catalepsy - metabolism Cell receptors Cell structures and functions Cellular signal transduction Chimera Dopamine - metabolism Dopamine Agonists - pharmacology Dopamine Antagonists - pharmacology Dopamine receptors Drug abuse Drug therapy Drugs Fundamental and applied biological sciences. Psychology Genetic aspects Genetics Haloperidol - pharmacology Humanities and Social Sciences letter Life Sciences Mental disorders Mental illness Mice Mice, Inbred C57BL Mice, Knockout Molecular and cellular biology Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine) multidisciplinary Mutagenesis Neurology Physiological aspects Postsynaptic potentials Protein Isoforms - chemistry Protein Isoforms - physiology Quinpirole - pharmacology Receptors, Dopamine D2 - chemistry Receptors, Dopamine D2 - genetics Receptors, Dopamine D2 - physiology Science Science (multidisciplinary) Signal Transduction Spiperone - pharmacology Synapses - physiology |
| title | Distinct functions of the two isoforms of dopamine D2 receptors |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T17%3A31%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Distinct%20functions%20of%20the%20two%20isoforms%20of%20dopamine%20D2%20receptors&rft.jtitle=Nature%20(London)&rft.au=Usiello,%20Alessandro&rft.date=2000-11-09&rft.volume=408&rft.issue=6809&rft.spage=199&rft.epage=203&rft.pages=199-203&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/35041572&rft_dat=%3Cgale_hal_p%3EA218529969%3C/gale_hal_p%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c6202-421c1c5ae6176af4b54ac06bebcb2baebf39e798b82fc970dbd1f167a2afe28b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=204473471&rft_id=info:pmid/11089973&rft_galeid=A218529969&rfr_iscdi=true |