Eintrag weiter verarbeiten
Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions
Gespeichert in:
| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | Proceedings of the National Academy of Sciences, 106, 2009, 12, S. 4917-4922 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
|
| Schlagwörter: |
| author_facet |
Pan, Ying-Xian Xu, Jin Xu, Mingming Rossi, Grace C. Matulonis, Joshua E. Pasternak, Gavril W. Pan, Ying-Xian Xu, Jin Xu, Mingming Rossi, Grace C. Matulonis, Joshua E. Pasternak, Gavril W. |
|---|---|
| author |
Pan, Ying-Xian Xu, Jin Xu, Mingming Rossi, Grace C. Matulonis, Joshua E. Pasternak, Gavril W. |
| spellingShingle |
Pan, Ying-Xian Xu, Jin Xu, Mingming Rossi, Grace C. Matulonis, Joshua E. Pasternak, Gavril W. Proceedings of the National Academy of Sciences Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions Multidisciplinary |
| author_sort |
pan, ying-xian |
| spelling |
Pan, Ying-Xian Xu, Jin Xu, Mingming Rossi, Grace C. Matulonis, Joshua E. Pasternak, Gavril W. 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0811586106 <jats:p>Heroin remains a major drug of abuse and is preferred by addicts over morphine. Like morphine, heroin has high affinity and selectivity for μ-receptors, but its residual analgesia in exon 1 MOR-1 knockout mice that do not respond to morphine suggests a different mechanism of action. MOR-1 splice variants lacking exon 1 have been observed in mice, humans, and rats, raising the possibility that they might be responsible for the residual heroin and morphine-6β-glucuronide (M6G) analgesia in the exon 1 knockout mice. To test this possibility, we disrupted exon 11 of MOR-1, which eliminates all of the variants that do not contain exon 1. Morphine and methadone analgesia in the exon 11 knockout mouse was normal, but the analgesic actions of heroin, M6G, and fentanyl were markedly diminished in the radiant heat tail-flick and hot-plate assays. Similarly, the ability of M6G to inhibit gastrointestinal transit was greatly diminished in these exon 11 knockout mice, whereas the ability of morphine was unchanged. These findings identify receptors selectively involved with heroin and M6G actions and confirm the relevance of the exon 11-associated variants and raise important issues regarding the importance of atypical truncated G-protein-coupled receptors.</jats:p> Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions Proceedings of the National Academy of Sciences |
| doi_str_mv |
10.1073/pnas.0811586106 |
| facet_avail |
Online Free |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA3My9wbmFzLjA4MTE1ODYxMDY |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA3My9wbmFzLjA4MTE1ODYxMDY |
| institution |
DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 |
| imprint |
Proceedings of the National Academy of Sciences, 2009 |
| imprint_str_mv |
Proceedings of the National Academy of Sciences, 2009 |
| issn |
0027-8424 1091-6490 |
| issn_str_mv |
0027-8424 1091-6490 |
| language |
English |
| mega_collection |
Proceedings of the National Academy of Sciences (CrossRef) |
| match_str |
pan2009involvementofexon11associatedvariantsofthemuopioidreceptormor1inheroinbutnotmorphineactions |
| publishDateSort |
2009 |
| publisher |
Proceedings of the National Academy of Sciences |
| recordtype |
ai |
| record_format |
ai |
| series |
Proceedings of the National Academy of Sciences |
| source_id |
49 |
| title |
Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_unstemmed |
Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_full |
Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_fullStr |
Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_full_unstemmed |
Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_short |
Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_sort |
involvement of exon 11-associated variants of the mu opioid receptor mor-1 in heroin, but not morphine, actions |
| topic |
Multidisciplinary |
| url |
http://dx.doi.org/10.1073/pnas.0811586106 |
| publishDate |
2009 |
| physical |
4917-4922 |
| description |
<jats:p>Heroin remains a major drug of abuse and is preferred by addicts over morphine. Like morphine, heroin has high affinity and selectivity for μ-receptors, but its residual analgesia in exon 1 MOR-1 knockout mice that do not respond to morphine suggests a different mechanism of action. MOR-1 splice variants lacking exon 1 have been observed in mice, humans, and rats, raising the possibility that they might be responsible for the residual heroin and morphine-6β-glucuronide (M6G) analgesia in the exon 1 knockout mice. To test this possibility, we disrupted exon 11 of MOR-1, which eliminates all of the variants that do not contain exon 1. Morphine and methadone analgesia in the exon 11 knockout mouse was normal, but the analgesic actions of heroin, M6G, and fentanyl were markedly diminished in the radiant heat tail-flick and hot-plate assays. Similarly, the ability of M6G to inhibit gastrointestinal transit was greatly diminished in these exon 11 knockout mice, whereas the ability of morphine was unchanged. These findings identify receptors selectively involved with heroin and M6G actions and confirm the relevance of the exon 11-associated variants and raise important issues regarding the importance of atypical truncated G-protein-coupled receptors.</jats:p> |
| container_issue |
12 |
| container_start_page |
4917 |
| container_title |
Proceedings of the National Academy of Sciences |
| container_volume |
106 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792341224027324416 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T16:16:28.6Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Involvement+of+exon+11-associated+variants+of+the+mu+opioid+receptor+MOR-1+in+heroin%2C+but+not+morphine%2C+actions&rft.date=2009-03-24&genre=article&issn=1091-6490&volume=106&issue=12&spage=4917&epage=4922&pages=4917-4922&jtitle=Proceedings+of+the+National+Academy+of+Sciences&atitle=Involvement+of+exon+11-associated+variants+of+the+mu+opioid+receptor+MOR-1+in+heroin%2C+but+not+morphine%2C+actions&aulast=Pasternak&aufirst=Gavril+W.&rft_id=info%3Adoi%2F10.1073%2Fpnas.0811586106&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792341224027324416 |
| author | Pan, Ying-Xian, Xu, Jin, Xu, Mingming, Rossi, Grace C., Matulonis, Joshua E., Pasternak, Gavril W. |
| author_facet | Pan, Ying-Xian, Xu, Jin, Xu, Mingming, Rossi, Grace C., Matulonis, Joshua E., Pasternak, Gavril W., Pan, Ying-Xian, Xu, Jin, Xu, Mingming, Rossi, Grace C., Matulonis, Joshua E., Pasternak, Gavril W. |
| author_sort | pan, ying-xian |
| container_issue | 12 |
| container_start_page | 4917 |
| container_title | Proceedings of the National Academy of Sciences |
| container_volume | 106 |
| description | <jats:p>Heroin remains a major drug of abuse and is preferred by addicts over morphine. Like morphine, heroin has high affinity and selectivity for μ-receptors, but its residual analgesia in exon 1 MOR-1 knockout mice that do not respond to morphine suggests a different mechanism of action. MOR-1 splice variants lacking exon 1 have been observed in mice, humans, and rats, raising the possibility that they might be responsible for the residual heroin and morphine-6β-glucuronide (M6G) analgesia in the exon 1 knockout mice. To test this possibility, we disrupted exon 11 of MOR-1, which eliminates all of the variants that do not contain exon 1. Morphine and methadone analgesia in the exon 11 knockout mouse was normal, but the analgesic actions of heroin, M6G, and fentanyl were markedly diminished in the radiant heat tail-flick and hot-plate assays. Similarly, the ability of M6G to inhibit gastrointestinal transit was greatly diminished in these exon 11 knockout mice, whereas the ability of morphine was unchanged. These findings identify receptors selectively involved with heroin and M6G actions and confirm the relevance of the exon 11-associated variants and raise important issues regarding the importance of atypical truncated G-protein-coupled receptors.</jats:p> |
| doi_str_mv | 10.1073/pnas.0811586106 |
| facet_avail | Online, Free |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA3My9wbmFzLjA4MTE1ODYxMDY |
| imprint | Proceedings of the National Academy of Sciences, 2009 |
| imprint_str_mv | Proceedings of the National Academy of Sciences, 2009 |
| institution | DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275 |
| issn | 0027-8424, 1091-6490 |
| issn_str_mv | 0027-8424, 1091-6490 |
| language | English |
| last_indexed | 2024-03-01T16:16:28.6Z |
| match_str | pan2009involvementofexon11associatedvariantsofthemuopioidreceptormor1inheroinbutnotmorphineactions |
| mega_collection | Proceedings of the National Academy of Sciences (CrossRef) |
| physical | 4917-4922 |
| publishDate | 2009 |
| publishDateSort | 2009 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | ai |
| recordtype | ai |
| series | Proceedings of the National Academy of Sciences |
| source_id | 49 |
| spelling | Pan, Ying-Xian Xu, Jin Xu, Mingming Rossi, Grace C. Matulonis, Joshua E. Pasternak, Gavril W. 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0811586106 <jats:p>Heroin remains a major drug of abuse and is preferred by addicts over morphine. Like morphine, heroin has high affinity and selectivity for μ-receptors, but its residual analgesia in exon 1 MOR-1 knockout mice that do not respond to morphine suggests a different mechanism of action. MOR-1 splice variants lacking exon 1 have been observed in mice, humans, and rats, raising the possibility that they might be responsible for the residual heroin and morphine-6β-glucuronide (M6G) analgesia in the exon 1 knockout mice. To test this possibility, we disrupted exon 11 of MOR-1, which eliminates all of the variants that do not contain exon 1. Morphine and methadone analgesia in the exon 11 knockout mouse was normal, but the analgesic actions of heroin, M6G, and fentanyl were markedly diminished in the radiant heat tail-flick and hot-plate assays. Similarly, the ability of M6G to inhibit gastrointestinal transit was greatly diminished in these exon 11 knockout mice, whereas the ability of morphine was unchanged. These findings identify receptors selectively involved with heroin and M6G actions and confirm the relevance of the exon 11-associated variants and raise important issues regarding the importance of atypical truncated G-protein-coupled receptors.</jats:p> Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions Proceedings of the National Academy of Sciences |
| spellingShingle | Pan, Ying-Xian, Xu, Jin, Xu, Mingming, Rossi, Grace C., Matulonis, Joshua E., Pasternak, Gavril W., Proceedings of the National Academy of Sciences, Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions, Multidisciplinary |
| title | Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_full | Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_fullStr | Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_full_unstemmed | Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_short | Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| title_sort | involvement of exon 11-associated variants of the mu opioid receptor mor-1 in heroin, but not morphine, actions |
| title_unstemmed | Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.0811586106 |