PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33555037-7 2021 KEY RESULTS: Morphine, PZM21 and TRV130 were partial agonists in the beta-arrestin2 recruitment assay. Morphine 13-21 arrestin, beta 2 Mus musculus 69-83 34031190-6 2021 With the degradation of beta-arrestin2, ABIN-1 overexpression also decreased MOR phosphorylation and internalization following opioid treatment, affecting the beta-arrestin2-dependent signaling pathway to regulate morphine tolerance. Morphine 214-222 arrestin, beta 2 Mus musculus 159-173 34031190-7 2021 Importantly, the effect of ABIN-1 on morphine tolerance was abolished in beta-arrestin2 knockout mice. Morphine 37-45 arrestin, beta 2 Mus musculus 73-87 34031190-8 2021 Taken together, these results suggest that the interaction between ABIN-1 and beta-arrestin2 inhibits MOR internalization to attenuate morphine tolerance, revealing a novel mechanism for MOR regulation. Morphine 135-143 arrestin, beta 2 Mus musculus 78-92 34031190-12 2021 ABIN-1 targeted beta-arrestin2 to regulate morphine tolerance Therefore, inhibiting of ABIN-1 is an important strategy to prevent morphine tolerance and dependence. Morphine 43-51 arrestin, beta 2 Mus musculus 16-30 34031190-12 2021 ABIN-1 targeted beta-arrestin2 to regulate morphine tolerance Therefore, inhibiting of ABIN-1 is an important strategy to prevent morphine tolerance and dependence. Morphine 130-138 arrestin, beta 2 Mus musculus 16-30 33705801-5 2021 Whole-cell current-clamp electrophysiology experiments revealed that 15-18-h overnight exposure to 10 muM morphine in vitro induced acute tolerance in beta-arrestin-2 wild-type but not knockout neurons. Morphine 106-114 arrestin, beta 2 Mus musculus 151-166 33705801-7 2021 Similarly, acute morphine tolerance in vivo in beta-arrestin-2 knockout mice was prevented in the warm-water tail-withdrawal assay. Morphine 17-25 arrestin, beta 2 Mus musculus 47-62 33705801-9 2021 Alternately, in beta-arrestin-2 knockout neurons tolerance induced by 7-day in vivo exposure to 50 mg morphine pellet was conserved. Morphine 102-110 arrestin, beta 2 Mus musculus 16-31 28820778-3 2017 The multifunctional protein beta-arrestin2 regulates the hedonic effects of morphine and participates in tolerance. Morphine 76-84 arrestin, beta 2 Mus musculus 28-42 31057409-1 2019 Between 2000 and 2005 several studies revealed that morphine is more potent and exhibits fewer side effects in beta-arrestin 2 knockout mice. Morphine 52-60 arrestin, beta 2 Mus musculus 111-126 29713080-0 2018 Complex formation between the vasopressin 1b receptor, beta-arrestin-2, and the mu-opioid receptor underlies morphine tolerance. Morphine 109-117 arrestin, beta 2 Mus musculus 55-70 32854452-3 2020 Studies in beta-arrestin 2 gene knockout (betaarr2(-/-)) animals indicate that morphine analgesia is potentiated while side effects are reduced, suggesting that drugs biased away from arrestin may manifest with a reduced-side-effect profile. Morphine 79-87 arrestin, beta 2 Mus musculus 42-50 28855588-0 2017 Morphine activation of mu opioid receptors causes disinhibition of neurons in the ventral tegmental area mediated by beta-arrestin2 and c-Src. Morphine 0-8 arrestin, beta 2 Mus musculus 117-131 28855588-9 2017 Inhibition of IPSC frequency by morphine was also reduced in beta-arr2-/- neurons in which PP2 caused no further reduction. Morphine 32-40 arrestin, beta 2 Mus musculus 61-70 28855588-10 2017 These data suggest that inhibition of IPSCs by morphine involves a beta-arr2/c-Src mediated mechanism. Morphine 47-55 arrestin, beta 2 Mus musculus 67-76 23960234-9 2013 Morphine pretreatment provoked a marked increase in the formation of a molecular complex composed of TRAF6 and beta-arrestin-2. Morphine 0-8 arrestin, beta 2 Mus musculus 111-126 28391016-3 2017 In mice, morphine administration induces hypermotility and this response has been described in terms of a beta-arrestin2-dependent mechanism that favors prevalent dopamine D1 receptor activation. Morphine 9-17 arrestin, beta 2 Mus musculus 106-120 28319053-8 2017 In cell-based studies, exon 7-associated variants shifted the bias of several mu opioids toward beta-arrestin 2 over G protein activation compared with the exon 4-associated variant, suggesting an interaction of exon 7-associated C-terminal tails with beta-arrestin 2 in morphine-induced desensitization and tolerance. Morphine 271-279 arrestin, beta 2 Mus musculus 96-111 28319053-8 2017 In cell-based studies, exon 7-associated variants shifted the bias of several mu opioids toward beta-arrestin 2 over G protein activation compared with the exon 4-associated variant, suggesting an interaction of exon 7-associated C-terminal tails with beta-arrestin 2 in morphine-induced desensitization and tolerance. Morphine 271-279 arrestin, beta 2 Mus musculus 252-267 24597632-1 2015 BACKGROUND AND PURPOSE: Tolerance to the behavioural effects of morphine is blunted in beta-arrestin-2 knockout mice, but opioid withdrawal is largely unaffected. Morphine 64-72 arrestin, beta 2 Mus musculus 87-102 24555516-0 2015 Enhancement of morphine analgesia and prevention of morphine tolerance by downregulation of beta-arrestin 2 with antigene RNAs in mice. Morphine 15-23 arrestin, beta 2 Mus musculus 92-107 24555516-0 2015 Enhancement of morphine analgesia and prevention of morphine tolerance by downregulation of beta-arrestin 2 with antigene RNAs in mice. Morphine 52-60 arrestin, beta 2 Mus musculus 92-107 24555516-3 2015 In this study, antigene RNAs (agRNAs), which could selectively target gene transcription start sites and potently inhibit gene expression, were used to downregulate the expression of beta-arrestin 2 to investigate its effects on morphine analgesia and tolerance in mice. Morphine 229-237 arrestin, beta 2 Mus musculus 183-198 24555516-5 2015 Mice treated with beta-arrestin 2 agRNAs showed enhanced analgesic effects in response to morphine and failed to develop antinociceptive tolerance. Morphine 90-98 arrestin, beta 2 Mus musculus 18-33 24555516-6 2015 These results suggest that inhibition of beta-arrestin 2 in the brain with specific agRNAs can improve morphine efficacy, and consequently provide us a useful strategy for treatment of chronic intractable pain and morphine tolerance in vivo. Morphine 103-111 arrestin, beta 2 Mus musculus 41-56 24555516-6 2015 These results suggest that inhibition of beta-arrestin 2 in the brain with specific agRNAs can improve morphine efficacy, and consequently provide us a useful strategy for treatment of chronic intractable pain and morphine tolerance in vivo. Morphine 214-222 arrestin, beta 2 Mus musculus 41-56 25194025-0 2014 Morphine dependence in single enteric neurons from the mouse colon requires deletion of beta-arrestin2. Morphine 0-8 arrestin, beta 2 Mus musculus 88-102 25194025-8 2014 However, morphine-treated colonic neurons from beta-arrestin2 knockout mice demonstrated increased excitability upon treatment with naloxone as assessed by change in rheobase, number of action potentials and input resistance. Morphine 9-17 arrestin, beta 2 Mus musculus 47-61 25194025-10 2014 However, unlike the ileum, dependence to chronic exposure of morphine develops in colonic neurons from the beta-arrestin2 knockout mice. Morphine 61-69 arrestin, beta 2 Mus musculus 107-121 25194025-11 2014 These studies corroborate the in-vivo findings of the differential role of neuronal beta-arrestin2 in the development of morphine tolerance/dependence in the ileum and colon. Morphine 121-129 arrestin, beta 2 Mus musculus 84-98 25083714-2 2014 Previously we have shown that decreased expression of beta-arrestin2 upon chronic morphine is associated with the development of opioid tolerance in the gastrointestinal tract. Morphine 82-90 arrestin, beta 2 Mus musculus 54-68 27152166-4 2014 Unlike beta-arrestin1 (betaarr1)-deficient mice, mice globally deficient for beta-arrestin2 (betaarr2) mount a reduced hyperlocomotor response to either morphine or amphetamine. Morphine 153-161 arrestin, beta 2 Mus musculus 77-91 27152166-4 2014 Unlike beta-arrestin1 (betaarr1)-deficient mice, mice globally deficient for beta-arrestin2 (betaarr2) mount a reduced hyperlocomotor response to either morphine or amphetamine. Morphine 153-161 arrestin, beta 2 Mus musculus 93-101 24223972-7 2013 Sub-acute morphine administration resulted in a decrease of NMDAR1 and Arrb2 whereas during longer opioid treatment the expression NMDAR1 and Arrb2 mRNA increased again to baseline values. Morphine 10-18 arrestin, beta 2 Mus musculus 71-76 24223972-7 2013 Sub-acute morphine administration resulted in a decrease of NMDAR1 and Arrb2 whereas during longer opioid treatment the expression NMDAR1 and Arrb2 mRNA increased again to baseline values. Morphine 10-18 arrestin, beta 2 Mus musculus 142-147 24063433-3 2013 The classical mu opioid morphine elicited increased efficacy and duration of analgesic response with reduced side effects in beta-arrestin-2 knockout mice compared to wild-type mice, suggesting that G protein biased mu opioid receptor agonists would be more efficacious with reduced adverse events. Morphine 24-32 arrestin, beta 2 Mus musculus 125-140 23960234-11 2013 In conclusion, our results show that activation of mu and delta opioid receptors with morphine suppresses TLR4-induced TNF release in mast cells, preventing the IKK-dependent phosphorylation of SNAP-23, which is necessary for TNF exocytosis, and this inhibition correlates with the formation of a beta-arrestin-2/TRAF6 complex. Morphine 86-94 arrestin, beta 2 Mus musculus 297-312 22491351-6 2012 Indeed, two different JNK inhibitors reversed the enhanced analgesic effect of morphine, a known phenotype of beta-arr2-/- mice, to +/+ levels. Morphine 79-87 arrestin, beta 2 Mus musculus 110-119 23300227-2 2013 Morphine pharmacology in beta-arrestin-2 knockout mice suggested that a ligand that promotes coupling of the mu-opioid receptor (MOR) to G proteins, but not beta-arrestins, would result in higher analgesic efficacy, less gastrointestinal dysfunction, and less respiratory suppression than morphine. Morphine 0-8 arrestin, beta 2 Mus musculus 25-40 22491351-0 2012 Evidence that behavioral phenotypes of morphine in beta-arr2-/- mice are due to the unmasking of JNK signaling. Morphine 39-47 arrestin, beta 2 Mus musculus 51-60 22491351-1 2012 The altered behavioral effects of morphine, but not most other mu agonists, in mice lacking beta-arrestin 2, suggest that this scaffolding protein regulates the signaling cascade of this commonly used analgesic. Morphine 34-42 arrestin, beta 2 Mus musculus 92-107 22491351-2 2012 One of the cascades that could be regulated by beta-arrestin 2 is cJun-N-terminal kinase (JNK), which binds with beta-arrestin 2 and modulates the analgesic effects of morphine. Morphine 168-176 arrestin, beta 2 Mus musculus 47-62 22491351-2 2012 One of the cascades that could be regulated by beta-arrestin 2 is cJun-N-terminal kinase (JNK), which binds with beta-arrestin 2 and modulates the analgesic effects of morphine. Morphine 168-176 arrestin, beta 2 Mus musculus 113-128 22491351-7 2012 Both the reduced locomotor effect of morphine and the psychomotor sensitization to repeated morphine administration in beta-arr2-/- mice were also returned to +/+ levels by inhibiting JNK. Morphine 37-45 arrestin, beta 2 Mus musculus 119-128 22491351-7 2012 Both the reduced locomotor effect of morphine and the psychomotor sensitization to repeated morphine administration in beta-arr2-/- mice were also returned to +/+ levels by inhibiting JNK. Morphine 92-100 arrestin, beta 2 Mus musculus 119-128 22491351-9 2012 Furthermore, a PKC inhibitor had a similar effect as inhibiting JNK in reducing the enhanced analgesic effect of morphine in beta-arr2-/- mice to +/+ levels. Morphine 113-121 arrestin, beta 2 Mus musculus 125-134 19854889-1 2010 The agonists of mu-opioid receptor (OPRM1) induce extracellular signal-regulated kinase (ERK) phosphorylation through different pathways: morphine uses the protein kinase C (PKC)-pathway, whereas fentanyl functions in a beta-arrestin2-dependent manner. Morphine 138-146 arrestin, beta 2 Mus musculus 220-234 20980993-4 2011 Indeed, G protein-coupled receptor desensitization and adaptor protein beta-arrestin 2 (betaarr2) through its interaction with the mu-opioid receptor regulates the analgesic but not the rewarding properties of morphine. Morphine 210-218 arrestin, beta 2 Mus musculus 71-86 20980993-4 2011 Indeed, G protein-coupled receptor desensitization and adaptor protein beta-arrestin 2 (betaarr2) through its interaction with the mu-opioid receptor regulates the analgesic but not the rewarding properties of morphine. Morphine 210-218 arrestin, beta 2 Mus musculus 88-96 20980993-5 2011 However, betaarr2 is also required for morphine-induced locomotor activity in mice, but the exact cellular and molecular mechanisms that mediate this arrestin-dependent behavior are not understood. Morphine 39-47 arrestin, beta 2 Mus musculus 9-17 20980993-6 2011 In this study, we show that betaarr2 is required for morphine-induced locomotor activity in a dopamine D1 receptor (D1R)-dependent manner and that a betaarr2/phospho-ERK (betaarr2/pERK) signaling complex may mediate this behavior. Morphine 53-61 arrestin, beta 2 Mus musculus 28-36 20980993-8 2011 Acute morphine administration to mice promotes the formation of a betaarr2/pERK signaling complex. Morphine 6-14 arrestin, beta 2 Mus musculus 66-74 20980993-9 2011 Morphine-induced locomotor activity and formation of the betaarr2/pERK signaling complex is blunted in D1R knockout (D1-KO) mice and is presumably independent of D2 dopamine receptors. Morphine 0-8 arrestin, beta 2 Mus musculus 57-65 20980993-11 2011 Taken together, these results suggest a potential role for a D1R-dependent betaarr2/pERK signaling complex in selectively mediating the locomotor-stimulating but not the rewarding properties of morphine. Morphine 194-202 arrestin, beta 2 Mus musculus 75-83 22129596-0 2012 The role of beta-arrestin2 in the mechanism of morphine tolerance in the mouse and guinea pig gastrointestinal tract. Morphine 47-55 arrestin, beta 2 Mus musculus 12-26 22129596-10 2012 A time-dependent decrease in the expression of beta-arrestin2 and extracellular signal-regulated kinase 1/2 occurred in the ileum but not the colon after 2 h of morphine (10 muM) exposure. Morphine 161-169 arrestin, beta 2 Mus musculus 47-61 22129596-13 2012 We conclude that a decrease in beta-arrestin2 is associated with tolerance development to morphine in the gastrointestinal tract. Morphine 90-98 arrestin, beta 2 Mus musculus 31-45 19497686-3 2009 In cell culture, overexpression of GRK6 facilitates morphine-induced beta-arrestin2 (betaarrestin2) recruitment and receptor internalization, suggesting that this kinase may play a role in regulating the microOR. Morphine 52-60 arrestin, beta 2 Mus musculus 69-83 19497686-3 2009 In cell culture, overexpression of GRK6 facilitates morphine-induced beta-arrestin2 (betaarrestin2) recruitment and receptor internalization, suggesting that this kinase may play a role in regulating the microOR. Morphine 52-60 arrestin, beta 2 Mus musculus 85-98 15346705-10 2004 Moreover, morphine tolerance can be completely reversed with a low dose of the classical PKC inhibitor chelerythrine in the beta-arrestin-2 knock-out, but not wild-type mice. Morphine 10-18 arrestin, beta 2 Mus musculus 124-139 19477204-5 2009 Co-treatment of human PBMC or murine splenocytes with gp120/morphine led to decreased expression of beta-arrestin 2, a protein required for opioid-mediated signaling. Morphine 60-68 arrestin, beta 2 Mus musculus 100-115 18558479-6 2008 However, although morphine also could induce a rapid desensitization on [Ca(2+)](i) release to a greater extent than that of DAMGO and could induce the phosphorylation of Ser(375) residue, morphine-induced desensitization was not influenced by mutating the phosphorylation sites or in MEF cells lacking betaArr1 and 2. Morphine 18-26 arrestin, beta 2 Mus musculus 303-317 17090705-7 2007 Studies in mice have shown that beta-arrestin-2 plays an important role in the development of morphine-induced tolerance, constipation, and respiratory depression. Morphine 94-102 arrestin, beta 2 Mus musculus 32-47 15917400-0 2005 Morphine side effects in beta-arrestin 2 knockout mice. Morphine 0-8 arrestin, beta 2 Mus musculus 25-40 15917400-4 2005 We have previously reported that mice lacking the G protein-coupled receptor regulatory protein, beta-arrestin 2, display profoundly altered morphine responses. Morphine 141-149 arrestin, beta 2 Mus musculus 97-112 15917400-5 2005 beta-Arrestin 2 knockout mice have enhanced and prolonged morphine analgesia with very little morphine tolerance. Morphine 58-66 arrestin, beta 2 Mus musculus 0-15 15917400-5 2005 beta-Arrestin 2 knockout mice have enhanced and prolonged morphine analgesia with very little morphine tolerance. Morphine 94-102 arrestin, beta 2 Mus musculus 0-15 19399231-0 2009 Improvement of morphine-mediated analgesia by inhibition of beta-arrestin2 expression in mice periaqueductal gray matter. Morphine 15-23 arrestin, beta 2 Mus musculus 60-74 19399231-2 2009 Here, we show that specific inhibition of beta-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. Morphine 184-192 arrestin, beta 2 Mus musculus 42-56 19399231-4 2009 These findings suggest that specific siRNA targeting beta-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance. Morphine 101-109 arrestin, beta 2 Mus musculus 53-67 17494695-2 2007 In beta-arrestin2-/- (beta arr2-/-) mice, a complex phenotype is observed that includes altered sensitivity to morphine. Morphine 111-119 arrestin, beta 2 Mus musculus 3-17 17494695-2 2007 In beta-arrestin2-/- (beta arr2-/-) mice, a complex phenotype is observed that includes altered sensitivity to morphine. Morphine 111-119 arrestin, beta 2 Mus musculus 22-35 17494695-5 2007 A lack of beta-arrestin2 reduced the maximum inhibition of VGCCs by morphine and DAMGO (D-Ala2-N-Me-Phe4-glycol5-enkephalin) without affecting agonist potency, the onset of receptor desensitization, or the functional contribution of N-type VGCCs. Morphine 68-76 arrestin, beta 2 Mus musculus 10-24 15788776-9 2005 These results suggest that induction of DOPr-mediated actions in PAG by chronic morphine requires prolonged MOPr stimulation and expression of beta-arrestin-2. Morphine 80-88 arrestin, beta 2 Mus musculus 143-158 10617462-0 1999 Enhanced morphine analgesia in mice lacking beta-arrestin 2. Morphine 9-17 arrestin, beta 2 Mus musculus 44-59 14614085-0 2003 Enhanced rewarding properties of morphine, but not cocaine, in beta(arrestin)-2 knock-out mice. Morphine 33-41 arrestin, beta 2 Mus musculus 63-79 14614085-4 2003 Mice lacking beta(arrestin)-2 (beta(arr2)) display enhanced sensitivity to morphine in tests of pain perception attributable to impaired desensitization of muOR. Morphine 75-83 arrestin, beta 2 Mus musculus 13-29 14614085-4 2003 Mice lacking beta(arrestin)-2 (beta(arr2)) display enhanced sensitivity to morphine in tests of pain perception attributable to impaired desensitization of muOR. Morphine 75-83 arrestin, beta 2 Mus musculus 31-40 14614085-8 2003 However, in the beta(arr2)-KO mice, morphine induced more pronounced increases in striatal extracellular dopamine than in WT mice. Morphine 36-44 arrestin, beta 2 Mus musculus 16-25 14614085-9 2003 Moreover, the rewarding properties of morphine in the conditioned place preference test were greater in the beta(arr2)-KO mice when compared with the WT mice. Morphine 38-46 arrestin, beta 2 Mus musculus 108-117 14614085-10 2003 Thus, beta(arr2) appears to play a more important role in the dopaminergic effects mediated by morphine than those induced by cocaine. Morphine 95-103 arrestin, beta 2 Mus musculus 6-15 12451149-0 2002 Differential mechanisms of morphine antinociceptive tolerance revealed in (beta)arrestin-2 knock-out mice. Morphine 27-35 arrestin, beta 2 Mus musculus 75-90 12451149-3 2002 We have shown previously that mice lacking (beta)arr2 experience enhanced morphine-induced analgesia and do not become tolerant to morphine as determined in the hot-plate test, a paradigm that primarily assesses supraspinal pain responsiveness. Morphine 74-82 arrestin, beta 2 Mus musculus 44-53 12451149-5 2002 In this test, the (beta)arr2-KO mice have greater basal nociceptive thresholds and markedly enhanced sensitivity to morphine. Morphine 116-124 arrestin, beta 2 Mus musculus 19-28 12451149-7 2002 In the (beta)arr2-KO but not WT mice, morphine tolerance can be completely reversed with a low dose of the classical protein kinase C (PKC) inhibitor chelerythrine. Morphine 38-46 arrestin, beta 2 Mus musculus 8-17 12451149-9 2002 Furthermore, although (beta)arr2 appears to be the most prominent and proximal determinant of muOR desensitization and morphine tolerance, in the absence of this mechanism, the contributions of a PKC-dependent regulatory system become readily apparent. Morphine 119-127 arrestin, beta 2 Mus musculus 23-32 11130073-0 2000 Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Morphine 65-73 arrestin, beta 2 Mus musculus 38-53 10617462-3 1999 Functional deletion of the beta-arrestin 2 gene in mice resulted in remarkable potentiation and prolongation of the analgesic effect of morphine, suggesting that muOR desensitization was impaired. Morphine 136-144 arrestin, beta 2 Mus musculus 27-42 10617462-5 1999 Moreover, they suggest that inhibition of beta-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic tolerance, and dependence. Morphine 117-125 arrestin, beta 2 Mus musculus 42-57