ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression
Opioids are perhaps the most effective analgesics in medicine. However, between 1999 and 2018, over 400,000 people in the United States died from opioid overdose. Excessive opioids make breathing lethally slow and shallow, a side-effect called opioid-induced respiratory depression. This doubled-edge...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/62552 |
| _version_ | 1811199242648158208 |
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| author | Iris Bachmutsky Xin Paul Wei Adelae Durand Kevin Yackle |
| author_facet | Iris Bachmutsky Xin Paul Wei Adelae Durand Kevin Yackle |
| author_sort | Iris Bachmutsky |
| collection | DOAJ |
| description | Opioids are perhaps the most effective analgesics in medicine. However, between 1999 and 2018, over 400,000 people in the United States died from opioid overdose. Excessive opioids make breathing lethally slow and shallow, a side-effect called opioid-induced respiratory depression. This doubled-edged sword has sparked the desire to develop novel therapeutics that provide opioid-like analgesia without depressing breathing. One such approach has been the design of so-called ‘biased agonists’ that signal through some, but not all pathways downstream of the µ-opioid receptor (MOR), the target of morphine and other opioid analgesics. This rationale stems from a study suggesting that MOR-induced ß-arrestin 2 dependent signaling is responsible for opioid respiratory depression, whereas adenylyl cyclase inhibition produces analgesia. To verify this important result that motivated the ‘biased agonist’ approach, we re-examined breathing in ß-arrestin 2-deficient mice and instead find no connection between ß-arrestin 2 and opioid respiratory depression. This result suggests that any attenuated effect of ‘biased agonists’ on breathing is through an as-yet defined mechanism. |
| first_indexed | 2024-04-12T01:44:45Z |
| format | Article |
| id | doaj.art-3d779d06f0444987a64d0cd42796b504 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:44:45Z |
| publishDate | 2021-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3d779d06f0444987a64d0cd42796b5042022-12-22T03:53:06ZengeLife Sciences Publications LtdeLife2050-084X2021-05-011010.7554/eLife.62552ß-arrestin 2 germline knockout does not attenuate opioid respiratory depressionIris Bachmutsky0Xin Paul Wei1https://orcid.org/0000-0002-6621-3143Adelae Durand2Kevin Yackle3https://orcid.org/0000-0003-1870-2759Department of Physiology, University of California, San Francisco, San Francisco, United States; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United StatesDepartment of Physiology, University of California, San Francisco, San Francisco, United States; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, United StatesDepartment of Physiology, University of California, San Francisco, San Francisco, United StatesDepartment of Physiology, University of California, San Francisco, San Francisco, United StatesOpioids are perhaps the most effective analgesics in medicine. However, between 1999 and 2018, over 400,000 people in the United States died from opioid overdose. Excessive opioids make breathing lethally slow and shallow, a side-effect called opioid-induced respiratory depression. This doubled-edged sword has sparked the desire to develop novel therapeutics that provide opioid-like analgesia without depressing breathing. One such approach has been the design of so-called ‘biased agonists’ that signal through some, but not all pathways downstream of the µ-opioid receptor (MOR), the target of morphine and other opioid analgesics. This rationale stems from a study suggesting that MOR-induced ß-arrestin 2 dependent signaling is responsible for opioid respiratory depression, whereas adenylyl cyclase inhibition produces analgesia. To verify this important result that motivated the ‘biased agonist’ approach, we re-examined breathing in ß-arrestin 2-deficient mice and instead find no connection between ß-arrestin 2 and opioid respiratory depression. This result suggests that any attenuated effect of ‘biased agonists’ on breathing is through an as-yet defined mechanism.https://elifesciences.org/articles/62552Opioidsopioid induced respiratory depressionbiased agonistß-arrestin 2breathing |
| spellingShingle | Iris Bachmutsky Xin Paul Wei Adelae Durand Kevin Yackle ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression eLife Opioids opioid induced respiratory depression biased agonist ß-arrestin 2 breathing |
| title | ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression |
| title_full | ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression |
| title_fullStr | ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression |
| title_full_unstemmed | ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression |
| title_short | ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression |
| title_sort | ss arrestin 2 germline knockout does not attenuate opioid respiratory depression |
| topic | Opioids opioid induced respiratory depression biased agonist ß-arrestin 2 breathing |
| url | https://elifesciences.org/articles/62552 |
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