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Reverse of Acute and Chronic Morphine Tolerance by Lithocholic Acid via Down-Regulating UGT2B7

Overview of attention for article published in Frontiers in Pharmacology, November 2016
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Title
Reverse of Acute and Chronic Morphine Tolerance by Lithocholic Acid via Down-Regulating UGT2B7
Published in
Frontiers in Pharmacology, November 2016
DOI 10.3389/fphar.2016.00404
Pubmed ID
Authors

Zizhao Yang, Li Li, Haihong Hu, Mingcheng Xu, Jingkai Gu, Zaijie Jim Wang, Lushan Yu, Su Zeng

Abstract

Lithocholic acid (LCA) deposited in human livers always induces drastic pains which need analgesic drug, like morphine to release. Our research showed that LCA can effectively inhibit uridine 5'-diphospho-glucuronosyltransferase 2B7 (UGT2B7) in morphine tolerance-like human normal liver cells, HL-7702, then increase μ-opioid receptor (MOR) and calcium-calmodulin dependent protein kinase IIα (CaMKIIα) expression. In vivo assay, UGT2B7 was significantly repressed in the livers of acute or chronic morphine tolerance mice pretreated with LCA (10, 50, and 100 mg/kg, p.o.). To investigate the connections between LCA function performance and change of UGT2B7 enzymatic activity in mice livers, two morphine metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were quantified by solid phase extraction (SPE)-HPLC-MS/MS. The result indicated no matter in acute or chronic morphine tolerance, the concentrations of M3G and M6G were all decreased, the later one fell even more. Besides that, 50 mg/kg of LCA administration can prevent auto-phosphorylation of CaMKIIα at Thr286 in acute or chronic morphine tolerance mice prefrontal cortexes (mPFCs) due to synthesis increase of cyclic adenosine monophosphate. As a consequence, UGT2B7 depression mediated by LCA can affect its selective catalysis ability to morphine, that may be responsible to acute or chronic morphine tolerance alleviation. These findings might assist to modify antinociception of morphine in clinic.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Belgium 1 7%
Unknown 13 93%

Demographic breakdown

Readers by professional status Count As %
Professor 4 29%
Student > Ph. D. Student 4 29%
Student > Bachelor 2 14%
Researcher 2 14%
Other 1 7%
Other 0 0%
Unknown 1 7%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 5 36%
Chemistry 2 14%
Business, Management and Accounting 1 7%
Biochemistry, Genetics and Molecular Biology 1 7%
Medicine and Dentistry 1 7%
Other 1 7%
Unknown 3 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 November 2016.
All research outputs
#20,349,664
of 22,896,955 outputs
Outputs from Frontiers in Pharmacology
#10,129
of 16,195 outputs
Outputs of similar age
#269,210
of 311,687 outputs
Outputs of similar age from Frontiers in Pharmacology
#96
of 161 outputs
Altmetric has tracked 22,896,955 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,195 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 161 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.