Abstract：
:Inflammatory bowel disease (IBD) is characterized by chronic, recurring inflammation of the digestive tract. Current therapeutic approaches are limited and include biologics and steroids such as anti-TNFα monoclonal antibodies and corticosteroids, respectively. Significant adverse drug effects can occur for chronic usage and include increased risk of infection in some patients. GPR4, a pH-sensing G protein-coupled receptor, has recently emerged as a potential therapeutic target for intestinal inflammation. We have assessed the effects of a GPR4 antagonist, 2-(4-((2-Ethyl-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)phenyl)-5-(piperidin-4-yl)-1,3,4-oxadiazole (GPR4 antagonist 13, also known as NE-52-QQ57) in the dextran sulfate sodium (DSS)-induced acute colitis mouse model. The GPR4 antagonist 13 inhibited intestinal inflammation. The clinical parameters such as body weight loss and fecal score were reduced in the GPR4 antagonist 13 treatment group compared to vehicle control. Macroscopic disease indicators such as colon shortening, splenic expansion, and mesenteric lymph node enlargement were all reduced in severity in the GPR4 antagonist 13 treated mice. Histopathological features of active colitis were alleviated in GPR4 antagonist 13 treatment groups compared to vehicle control. Finally, inflammatory gene expression in the colon tissues and vascular adhesion molecule expression in the intestinal endothelia were attenuated by GPR4 antagonist 13. Our results indicate that GPR4 antagonist 13 provides a protective effect in the DSS-induced acute colitis mouse model, and inhibition of GPR4 can be explored as a novel anti-inflammatory approach.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Sanderlin EJ,Marie M,Velcicky J,Loetscher P,Yang LVdoi
10.1016/j.ejphar.2019.03.038subject
Has Abstractpub_date
2019-06-05 00:00:00pages
218-230eissn
0014-2999issn
1879-0712pii
S0014-2999(19)30199-2journal_volume
852pub_type
杂志文章abstract：:Although the involvement of cannabinoids and the endogenous cannabinoid system in the regulation of the hypothalamo-pituitary-adrenal axis in rodents is well documented, the precise role played by the cannabinoid type one (CB(1)) receptor in this effect has not been fully elucidated. Consequently, we investigated the ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.08.083
更新日期：2006-12-03 00:00:00
abstract：:In rats, tolerance to the analgesic effect of intraventricular substance P (SP) develops quickly. In rats made tolerant to [D-Ala2, D-Leu5]enkephalin the analgesic efficacy of SP is reduced significantly. The latter result suggests some overlap in the sites of action of SP and [D-Ala2,D-Leu5] enkephalin. Since SP seem...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90119-5
更新日期：1984-02-10 00:00:00
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journal_title：European journal of pharmacology
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doi：10.1016/0014-2999(94)90393-x
更新日期：1994-01-14 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00709-8
更新日期：1999-12-03 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90281-2
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90396-0
更新日期：1979-04-15 00:00:00
abstract：:Glioma is a kind of lethal malignant tumor, and lacks efficient therapies. Combination therapy has been claimed to be a promising approach to combat cancer, due to its increased anti-cancer effects and reduced side effects. This study aimed to investigate the anti-cancer effect and mechanism of combining imatinib with...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173022
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abstract：:The regulation of acetylcholine (ACh) lifetime by acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BuChE, EC 3.1.1.8) was evaluated in vitro in canine tracheal smooth muscle preparations. Selective inhibition of AChE by low concentrations of 1,5-bis(N-allyl-N,N-dimethyl-4-ammoniumphenyl)-pentane-3-on...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90772-i
更新日期：1991-11-19 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00679-6
更新日期：1995-12-12 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90734-y
更新日期：1993-02-23 00:00:00
abstract：:It has been suggested that administration of a cannabinoid CB(1) (SR141716A ¿N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide) and CB(2) (SR144528 ¿N-[(1S)-endo-1, 3, 3-trimethyl bicyclo ¿2.2.1 heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyr azo le- 3-ca...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00226-0
更新日期：2000-05-19 00:00:00
abstract：:Three peptide components of atrial natriuretic factor (ANF) caused relaxation of carbachol-contracted guinea-pig isolated tracheal smooth muscle. These were the 1-28, 5-28 and 5-27 peptide sequences (ANF(1-28), ANF-(5-28) and ANF-(5-27)). The peptides were 10-30 times more potent in epithelium-denuded than in epitheli...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90328-2
更新日期：1992-03-03 00:00:00
abstract：:This study investigated the involvement of the opioid system in the antidepressant-like effect of adenosine in the forced swimming test. The effect of adenosine (10 mg/kg, i.p.) was prevented by the pretreatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist), naltrindole (3 mg/kg, i.p...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.08.026
更新日期：2007-12-08 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90022-4
更新日期：1976-05-01 00:00:00
abstract：:Transcriptional activation of the human CYP1A1 gene (coding for cytochrome P450 1A1) is mediated by the aryl hydrocarbon receptor. In the present study we have examined interaction of the ginsenoside Rg1 and Rb1 with the carcinogen activation pathway mediated by the aryl hydrocarbon receptor in HepG2 cells. RT-PCR was...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.10.057
更新日期：2008-12-28 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00651-2
更新日期：1999-11-03 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90445-4
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(95)90010-1
更新日期：1995-01-13 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.07.070
更新日期：2008-10-31 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90495-x
更新日期：1987-07-02 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(94)90172-4
更新日期：1994-04-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90026-e
更新日期：1993-12-21 00:00:00
abstract：:Our data indicate that sex steroids modify the number of GABA receptors, as detected by a [3H]muscimol binding assay, in the tuberoinfundibular GABAergic system. GABA binding was affected by chronic hormonal treatments in different ways depending on the sex of the rats and the steroids administered. Estradiol increase...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90416-5
更新日期：1988-10-11 00:00:00
