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...

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Autores principales:	Iris Bachmutsky, Xin Paul Wei, Adelae Durand, Kevin Yackle
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	Opioids opioid induced respiratory depression biased agonist ß-arrestin 2 breathing Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3d779d06f0444987a64d0cd42796b504
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spelling	oai:doaj.org-article:3d779d06f0444987a64d0cd42796b5042021-11-24T12:19:49Zß-arrestin 2 germline knockout does not attenuate opioid respiratory depression10.7554/eLife.625522050-084Xe62552https://doaj.org/article/3d779d06f0444987a64d0cd42796b5042021-05-01T00:00:00Zhttps://elifesciences.org/articles/62552https://doaj.org/toc/2050-084XOpioids 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.Iris BachmutskyXin Paul WeiAdelae DurandKevin YackleeLife Sciences Publications LtdarticleOpioidsopioid induced respiratory depressionbiased agonistß-arrestin 2breathingMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Opioids opioid induced respiratory depression biased agonist ß-arrestin 2 breathing Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	Opioids opioid induced respiratory depression biased agonist ß-arrestin 2 breathing Medicine R Science Q Biology (General) QH301-705.5 Iris Bachmutsky Xin Paul Wei Adelae Durand Kevin Yackle ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression
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.
format	article
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
title	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_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_sort	ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/3d779d06f0444987a64d0cd42796b504
work_keys_str_mv	AT irisbachmutsky ßarrestin2germlineknockoutdoesnotattenuateopioidrespiratorydepression AT xinpaulwei ßarrestin2germlineknockoutdoesnotattenuateopioidrespiratorydepression AT adelaedurand ßarrestin2germlineknockoutdoesnotattenuateopioidrespiratorydepression AT kevinyackle ßarrestin2germlineknockoutdoesnotattenuateopioidrespiratorydepression
_version_	1718415039839338496

ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression

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