{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:57:03Z","timestamp":1791619023460,"version":"4.3.4"},"reference-count":29,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA047978"],"award-info":[{"award-number":["R01DA047978"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R00DA038069"],"award-info":[{"award-number":["R00DA038069"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["F31DA053798"],"award-info":[{"award-number":["F31DA053798"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:p> Respiratory depression is a potentially fatal side effect of opioid analgesics and a major limitation to their use. G protein-biased opioid agonists have been proposed as \u201csafer\u201d analgesics with less respiratory depression. These agonists are biased to activate G proteins rather than \u03b2-arrestin signaling. Respiratory depression has been shown to correlate with both G protein bias and intrinsic efficacy, and recent work has refuted the role of \u03b2-arrestin signaling in opioid-induced respiratory depression. In addition, there is substantial evidence that G proteins do, in fact, mediate respiratory depression by actions in respiratory-controlling brainstem neurons. Based on these studies, we provide the perspective that protection from respiratory depression displayed by newly developed G protein-biased agonists is due to factors other than G protein versus arrestin bias. <\/jats:p>","DOI":"10.1152\/ajpcell.00259.2021","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T18:55:46Z","timestamp":1630522546000},"page":"C681-C683","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Evaluation of G protein bias and \u03b2-arrestin 2 signaling in opioid-induced respiratory depression"],"prefix":"10.1152","volume":"321","author":[{"given":"Jordan T.","family":"Bateman","sequence":"first","affiliation":[{"name":"Department of Pharmacology & Therapeutics, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3634-6594","authenticated-orcid":true,"given":"Erica S.","family":"Levitt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000004788"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6911a4"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200105000-00021"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1113\/JP278612"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5444.1566"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1113\/JP270822"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01407"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.06.001"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15580"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1956.tb00006.x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.173948"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1124\/pr.112.005942"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109237"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/35047086"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08162-1"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.087254"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.201616"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nature19112"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.035"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000003441"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14224"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaz3140"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aei145"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-021-01054-x"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7554\/elife.52694"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15004"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000984"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2020.09.009"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.10.020"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00259.2021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T15:52:22Z","timestamp":1718639542000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00259.2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,10,1]]}},"alternative-id":["10.1152\/ajpcell.00259.2021"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00259.2021","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]},"assertion":[{"value":"2021-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}