{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:07:50Z","timestamp":1761102470476,"version":"3.37.3"},"reference-count":54,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1124\/molpharm.121.000249","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T22:40:17Z","timestamp":1623883217000},"page":"217-223","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mice Expressing Regulators of G protein Signaling\u2013insensitive G\u03b1o Define Roles of \u03bc Opioid Receptor G\u03b1o and G\u03b1i Subunit Coupling in Inhibition of Presynaptic GABA Release"],"prefix":"10.1016","volume":"100","author":[{"given":"Courtney A.","family":"Bouchet","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kylie B.","family":"McPherson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"Traynor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan L.","family":"Ingram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1124\/molpharm.121.000249_bib1","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1038\/npp.2014.62","article-title":"Contribution of adenylyl cyclase modulation of pre- and postsynaptic GABA neurotransmission to morphine antinociception and tolerance","volume":"39","author":"Bobeck","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/molpharm.121.000249_bib2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1152\/jn.1998.79.2.677","article-title":"Endogenous opioid peptides acting at mu-opioid receptors in the dorsal horn contribute to midbrain modulation of spinal nociceptive neurons","volume":"79","author":"Budai","year":"1998","journal-title":"J Neurophysiol"},{"key":"10.1124\/molpharm.121.000249_bib3","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1046\/j.1471-4159.1995.64062534.x","article-title":"Expression of the mu-opioid receptor in CHO cells: ability of mu-opioid ligands to promote alpha-azidoanilido[32P]GTP labeling of multiple G protein alpha subunits","volume":"64","author":"Chakrabarti","year":"1995","journal-title":"J Neurochem"},{"key":"10.1124\/molpharm.121.000249_bib4","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0006-8993(86)90958-3","article-title":"Morphine microinjected into the periaqueductal gray has differential effects on 3 classes of medullary neurons","volume":"375","author":"Cheng","year":"1986","journal-title":"Brain Res"},{"key":"10.1124\/molpharm.121.000249_bib5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1476-5381.1994.tb16183.x","article-title":"Hyperpolarization by opioids acting on mu-receptors of a sub-population of rat periaqueductal gray neurones in vitro","volume":"113","author":"Chieng","year":"1994","journal-title":"Br J Pharmacol"},{"key":"10.1124\/molpharm.121.000249_bib6","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1124\/jpet.105.096818","article-title":"Comparison of the relative efficacy and potency of mu-opioid agonists to activate Galpha(i\/o) proteins containing a pertussis toxin-insensitive mutation","volume":"317","author":"Clark","year":"2006","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/molpharm.121.000249_bib7","doi-asserted-by":"crossref","first-page":"9418","DOI":"10.1074\/jbc.M208885200","article-title":"Endogenous RGS protein action modulates mu-opioid signaling through Galphao. Effects on adenylyl cyclase, extracellular signal-regulated kinases, and intracellular calcium pathways","volume":"278","author":"Clark","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000249_bib8","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1124\/mol.107.043547","article-title":"Endogenous regulators of G protein signaling differentially modulate full and partial mu-opioid agonists at adenylyl cyclase as predicted by a collision coupling model","volume":"73","author":"Clark","year":"2008","journal-title":"Mol Pharmacol"},{"key":"10.1124\/molpharm.121.000249_bib9","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1111\/j.1471-4159.2006.04176.x","article-title":"Mediation of adenylyl cyclase sensitization by PTX-insensitive GalphaoA, Galphai1, Galphai2 or Galphai3","volume":"99","author":"Clark","year":"2006","journal-title":"J Neurochem"},{"key":"10.1124\/molpharm.121.000249_bib10","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1046\/j.1440-1681.1999.03049.x","article-title":"Opioid receptor signalling mechanisms","volume":"26","author":"Connor","year":"1999","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"10.1124\/molpharm.121.000249_bib11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1469-7793.1998.047bo.x","article-title":"Modulation of Ca2+ channel currents of acutely dissociated rat periaqueductal grey neurons","volume":"509","author":"Connor","year":"1998","journal-title":"J Physiol"},{"key":"10.1124\/molpharm.121.000249_bib12","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.cobeha.2018.08.001","article-title":"Impact of sex on pain and opioid analgesia: a review","volume":"23","author":"Fullerton","year":"2018","journal-title":"Curr Opin Behav Sci"},{"key":"10.1124\/molpharm.121.000249_bib13","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1046\/j.1432-1327.1999.00301.x","article-title":"Nonselective coupling of the human mu-opioid receptor to multiple inhibitory G-protein isoforms","volume":"261","author":"Gaibelet","year":"1999","journal-title":"Eur J Biochem"},{"key":"10.1124\/molpharm.121.000249_bib14","first-page":"2557","article-title":"Influence of Gz and Gi2 transducer proteins in the affinity of opioid agonists to mu receptors","volume":"10","author":"Garz\u00f3n","year":"1998","journal-title":"Eur J Neurosci"},{"key":"10.1124\/molpharm.121.000249_bib15","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1038\/sj.npp.1300726","article-title":"The RGSZ2 protein exists in a complex with mu-opioid receptors and regulates the desensitizing capacity of Gz proteins","volume":"30","author":"Garz\u00f3n","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/molpharm.121.000249_bib16","doi-asserted-by":"crossref","first-page":"E2085","DOI":"10.1073\/pnas.1707887115","article-title":"Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt\/\u03b2-catenin pathway","volume":"115","author":"Gaspari","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/molpharm.121.000249_bib17","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/stke.2002.118.pl1","article-title":"G alpha COOH-terminal minigene vectors dissect heterotrimeric G protein signaling","volume":"2002","author":"Gilchrist","year":"2002","journal-title":"Sci STKE"},{"key":"10.1124\/molpharm.121.000249_bib18","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1124\/mol.108.054296","article-title":"Regulator of G protein signaling protein suppression of Galphao protein-mediated alpha2A adrenergic receptor inhibition of mouse hippocampal CA3 epileptiform activity","volume":"75","author":"Goldenstein","year":"2009","journal-title":"Mol Pharmacol"},{"key":"10.1124\/molpharm.121.000249_bib19","doi-asserted-by":"crossref","first-page":"4221","DOI":"10.1128\/MCB.25.10.4221-4228.2005","article-title":"Generation and characterization of Rgs4 mutant mice","volume":"25","author":"Grillet","year":"2005","journal-title":"Mol Cell Biol"},{"key":"10.1124\/molpharm.121.000249_bib20","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/325445a0","article-title":"The GTP-binding protein, Go, regulates neuronal calcium channels","volume":"325","author":"Hescheler","year":"1987","journal-title":"Nature"},{"key":"10.1124\/molpharm.121.000249_bib21","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1124\/pr.54.3.527","article-title":"Cellular regulation of RGS proteins: modulators and integrators of G protein signaling","volume":"54","author":"Hollinger","year":"2002","journal-title":"Pharmacol Rev"},{"key":"10.1124\/molpharm.121.000249_bib22","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1113\/jphysiol.1968.sp008495","article-title":"On the mechanism by which calcium and magnesium affect the release of transmitter by nerve impulses","volume":"196","author":"Hubbard","year":"1968","journal-title":"J Physiol"},{"key":"10.1124\/molpharm.121.000249_bib23","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/sj.npp.1301139","article-title":"Behavioral and electrophysiological evidence for opioid tolerance in adolescent rats","volume":"32","author":"Ingram","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/molpharm.121.000249_bib24","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1038\/sj.npp.1301634","article-title":"Tolerance to repeated morphine administration is associated with increased potency of opioid agonists","volume":"33","author":"Ingram","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/molpharm.121.000249_bib25","doi-asserted-by":"crossref","first-page":"10269","DOI":"10.1523\/JNEUROSCI.18-24-10269.1998","article-title":"Enhanced opioid efficacy in opioid dependence is caused by an altered signal transduction pathway","volume":"18","author":"Ingram","year":"1998","journal-title":"J Neurosci"},{"key":"10.1124\/molpharm.121.000249_bib26","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1038\/npp.2011.91","article-title":"\u03bc-Opioid receptor coupling to G\u03b1(o) plays an important role in opioid antinociception","volume":"36","author":"Lamberts","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/molpharm.121.000249_bib27","doi-asserted-by":"crossref","first-page":"4369","DOI":"10.1523\/JNEUROSCI.5470-12.2013","article-title":"Differential control of opioid antinociception to thermal stimuli in a knock-in mouse expressing regulator of G-protein signaling-insensitive G\u03b1o protein","volume":"33","author":"Lamberts","year":"2013","journal-title":"J Neurosci"},{"key":"10.1124\/molpharm.121.000249_bib28","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0896-6273(93)90314-H","article-title":"mu and delta opioid receptors differentially couple to G protein subtypes in membranes of human neuroblastoma SH-SY5Y cells","volume":"10","author":"Laugwitz","year":"1993","journal-title":"Neuron"},{"key":"10.1124\/molpharm.121.000249_bib29","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1111\/j.1460-9568.2008.06100.x","article-title":"Sexually dimorphic activation of the periaqueductal gray-rostral ventromedial medullary circuit during the development of tolerance to morphine in the rat","volume":"27","author":"Loyd","year":"2008","journal-title":"Eur J Neurosci"},{"key":"10.1124\/molpharm.121.000249_bib30","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/cne.20962","article-title":"Sex differences in the anatomical and functional organization of the periaqueductal gray-rostral ventromedial medullary pathway in the rat: a potential circuit mediating the sexually dimorphic actions of morphine","volume":"496","author":"Loyd","year":"2006","journal-title":"J Comp Neurol"},{"key":"10.1124\/molpharm.121.000249_bib31","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.expneurol.2014.04.004","article-title":"The neuroanatomy of sexual dimorphism in opioid analgesia","volume":"259","author":"Loyd","year":"2014","journal-title":"Exp Neurol"},{"key":"10.1124\/molpharm.121.000249_bib32","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0006-8993(91)90053-X","article-title":"Modification of morphine-induced analgesia and toxicity by pertussis toxin","volume":"544","author":"Lutfy","year":"1991","journal-title":"Brain Res"},{"key":"10.1124\/molpharm.121.000249_bib33","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1046\/j.1471-4159.2002.00946.x","article-title":"Agonists activate Gi1 alpha or Gi2 alpha fused to the human mu opioid receptor differently","volume":"81","author":"Massotte","year":"2002","journal-title":"J Neurochem"},{"key":"10.1124\/molpharm.121.000249_bib34","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.cell.2020.08.052","article-title":"A global map of G protein signaling regulation by RGS proteins","volume":"183","author":"Masuho","year":"2020","journal-title":"Cell"},{"key":"10.1124\/molpharm.121.000249_bib35","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1042\/bj2670391","article-title":"Delta-opioid-receptor-mediated inhibition of adenylate cyclase is transduced specifically by the guanine-nucleotide-binding protein Gi2","volume":"267","author":"McKenzie","year":"1990","journal-title":"Biochem J"},{"key":"10.1124\/molpharm.121.000249_bib36","doi-asserted-by":"crossref","first-page":"8737","DOI":"10.1523\/JNEUROSCI.0516-18.2018","article-title":"Regulators of G-protein signaling (RGS) proteins promote receptor coupling to G-protein-coupledinwardly rectifying potassium (GIRK) channels","volume":"38","author":"McPherson","year":"2018","journal-title":"J Neurosci"},{"key":"10.1124\/molpharm.121.000249_bib37","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/0020-711X(90)90004-M","article-title":"Guanine nucleotide binding proteins in neuroblastoma x glioma hybrid, NG108-15, cells. Regulation of expression and function","volume":"22","author":"Milligan","year":"1990","journal-title":"Int J Biochem"},{"key":"10.1124\/molpharm.121.000249_bib38","first-page":"157","article-title":"The role and specificity of guanine nucleotide binding proteins in receptor-effector coupling","volume":"44","author":"Milligan","year":"1990","journal-title":"Symp Soc Exp Biol"},{"key":"10.1124\/molpharm.121.000249_bib39","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1046\/j.1471-4159.2001.00196.x","article-title":"The human delta opioid receptor activates G(i1)alpha more efficiently than G(o1)alpha","volume":"76","author":"Moon","year":"2001","journal-title":"J Neurochem"},{"key":"10.1124\/molpharm.121.000249_bib40","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0006-8993(86)91367-3","article-title":"Evidence for GABA involvement in midbrain control of medullary neurons that modulate nociceptive transmission","volume":"397","author":"Moreau","year":"1986","journal-title":"Brain Res"},{"key":"10.1124\/molpharm.121.000249_bib41","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ejp.1513","article-title":"Differences in antinociceptive signalling mechanisms following morphine and fentanyl microinjections into the rat periaqueductal gray","volume":"24","author":"Morgan","year":"2020","journal-title":"Eur J Pain"},{"key":"10.1124\/molpharm.121.000249_bib42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/bs.pmbts.2015.04.010","article-title":"RGS-insensitive G proteins as in vivo probes of RGS function","volume":"133","author":"Neubig","year":"2015","journal-title":"Prog Mol Biol Transl Sci"},{"key":"10.1124\/molpharm.121.000249_bib43","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0014-2999(86)90240-2","article-title":"Pertussis toxin inhibits the antinociceptive action of morphine in the rat","volume":"124","author":"Parenti","year":"1986","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/molpharm.121.000249_bib44","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0014-2999(88)90732-7","article-title":"Pertussis toxin differentially reduces the efficacy of opioids to produce supraspinal analgesia in the mouse","volume":"152","author":"S\u00e1nchez-Bl\u00e1zquez","year":"1988","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/molpharm.121.000249_bib45","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/0091-3057(94)90101-5","article-title":"Spinal and supraspinal effects of pertussis toxin on opioid analgesia","volume":"49","author":"Shah","year":"1994","journal-title":"Pharmacol Biochem Behav"},{"key":"10.1124\/molpharm.121.000249_bib46","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/s41586-021-03507-1","article-title":"Structural basis of GABAB receptor-gi protein coupling","volume":"594","author":"Shen","year":"2021","journal-title":"Nature"},{"key":"10.1124\/molpharm.121.000249_bib47","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1124\/mi.5.1.7","article-title":"Regulators of G protein signaling & drugs of abuse","volume":"5","author":"Traynor","year":"2005","journal-title":"Mol Interv"},{"key":"10.1124\/molpharm.121.000249_bib48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1124\/mol.52.1.38","article-title":"Role of amino- and carboxyl-terminal regions of G(alphaZ) in the recognition of Gi-coupled receptors","volume":"52","author":"Tsu","year":"1997","journal-title":"Mol Pharmacol"},{"key":"10.1124\/molpharm.121.000249_bib49","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1113\/jphysiol.1997.sp021872","article-title":"Presynaptic inhibitory action of opioids on synaptic transmission in the rat periaqueductal grey in vitro","volume":"498","author":"Vaughan","year":"1997","journal-title":"J Physiol"},{"key":"10.1124\/molpharm.121.000249_bib50","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/37610","article-title":"How opioids inhibit GABA-mediated neurotransmission","volume":"390","author":"Vaughan","year":"1997","journal-title":"Nature"},{"key":"10.1124\/molpharm.121.000249_bib51","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1124\/pr.112.005942","article-title":"Regulation of \u03bc-opioid receptors: desensitization, phosphorylation, internalization, and tolerance","volume":"65","author":"Williams","year":"2013","journal-title":"Pharmacol Rev"},{"key":"10.1124\/molpharm.121.000249_bib52","doi-asserted-by":"crossref","first-page":"7278","DOI":"10.1074\/jbc.M208819200","article-title":"A spatial focusing model for G protein signals. Regulator of G protein signaling (RGS) protien-mediated kinetic scaffolding","volume":"278","author":"Zhong","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1124\/molpharm.121.000249_bib53","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1124\/mol.115.101600","article-title":"G\u03b2\u03b3 binds to the extreme C terminus of SNAP25 to mediate the action of Gi\/o-coupled G protein-coupled receptors","volume":"89","author":"Zurawski","year":"2016","journal-title":"Mol Pharmacol"},{"key":"10.1124\/molpharm.121.000249_bib54","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1126\/scisignal.aat8595","article-title":"Disabling the G\u03b2\u03b3-SNARE interaction disrupts GPCR-mediated presynaptic inhibition, leading to physiological and behavioral phenotypes","volume":"12","author":"Zurawski","year":"2019","journal-title":"Sci Signal"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24011507?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24011507?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/molpharm.121.000249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T08:46:29Z","timestamp":1739954789000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X24011507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["S0026895X24011507"],"URL":"https:\/\/doi.org\/10.1124\/molpharm.121.000249","relation":{},"ISSN":["0026-895X"],"issn-type":[{"type":"print","value":"0026-895X"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mice Expressing Regulators of G protein Signaling\u2013insensitive G\u03b1o Define Roles of \u03bc Opioid Receptor G\u03b1o and G\u03b1i Subunit Coupling in Inhibition of Presynaptic GABA Release","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/molpharm.121.000249","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}