A randomized, double-blind, placebo controlled, three-way crossover study exploring the efficacy of AZD3778 compared with placebo and an oral antihistamine (loratadine) in a model of seasonal allergic rhinitis - N/A

Start Date25 Sep 2005

Sponsor / Collaborator

AstraZeneca AB

100 Clinical Results associated with H1 receptor x CCR3

100 Translational Medicine associated with H1 receptor x CCR3

0 Patents (Medical) associated with H1 receptor x CCR3

Literatures (Medical) associated with H1 receptor x CCR3

13 Jan 2022·Evidence-Based Complementary and Alternative MedicineQ4 · MEDICINE

Acupuncture Alleviates Menstrual Pain in Rat Model via Suppressing Eotaxin/CCR3 Axis to Weak EOS-MC Activation

Q4 · MEDICINE

ArticleOA

Author: Wang, Jun-Xiang ; Qian, Xu ; Zhang, Zhou ; Ma, Liang-Xiao ; Sun, Tian-Yi ; Mu, Jie-Dan ; Tian, Yuan ; Yu, Wen-Yan

Introduction. Emerging data show that chemokine-mediated inflammation is involved in the occurrence and maintenance of pain. Recent evidence suggests that eotaxin levels rise when dysmenorrhea happens. The purpose of this study is to investigate whether eotaxin/CC chemokine receptor 3 (CCR3) axis, a key regulatory pathway for eosinophils (EOS) recruitment, is involved in acupuncture analgesia for dysmenorrhea. Methods. After the cold congealing dysmenorrhea (CCD) rat model prepared, animals received perpendicular needling (PN) and transverse needling (TN) at SP6, respectively, for 20 min. The CCR3 agonist CCL11 was administered 30 min prior to acupuncture. Pain behavior was assessed via a writhing response. The uterine contraction test was detected by an electrophysiological method. Eotaxin, histamine (HIS), and interleukin-6 (IL-6) levels were evaluated by ELISA. The expression of CCR3 and histamine H1 receptor (H1R) was analyzed by RT-qPCR and Western blot. The expression of EOS, mast cells (MCs), eosinophil peroxidase (EPO), and eosinophil cationic protein (ECP) was assessed by hematoxylin-eosin staining (HE), Toluidine Blue staining (TB), and immunohistochemistry, respectively. Results. Acupuncture prominently attenuated the menstrual pain in CCD rats, particularly TN technique. Electrophysiological recording data showed that the increased uterine contractility was ameliorated by acupuncture. In addition, TN decreased the release of eotaxin, HIS, IL-6, and the expression of CCR3 and H1R. HE, TB staining, and immunohistochemistry experiments showed that the increased expression of EOS, MCs, EPO, and ECP in uterine tissues was reversed by TN. Furthermore, we found that the effects of TN against CCD-induced menstrual pain, increased ECP expression, and HIS level were abolished by CCL11. Conclusion. TN alleviated menstrual pain by improving the uterine inflammatory environment via suppressing eotaxin/CCR3 axis to weak EOS-MC activation in CCD rats. The study findings support the acupuncture as a promising approach for dysmenorrhea, meanwhile, indicating the importance of performing appropriate needling technique.

01 Jun 2007·European Journal of PharmacologyQ3 · MEDICINE

A dual antagonist for chemokine CCR3 receptor and histamine H1 receptor

Q3 · MEDICINE

Article

Author: Tatsuaki Morokata ; Koichiro Takahashi ; Masayuki Kaneko ; Yasuaki Shimizu ; Ippei Sato ; Koichiro Morihira ; Satoko Takizawa ; Keiko Suzuki

Eosinophilic chemokines and histamine play distinct but important roles in allergic diseases. Inhibition of both eosinophilic chemokines and histamine, therefore, is an ideal strategy for the treatment of allergic inflammation, such as asthma, allergic rhinitis, and atopic dermatitis. YM-344484 was found to potently inhibit both the CCL11-induced Ca2+ influx in human CCR3-expressing cells (Kb=1.8 nM) and histamine-induced Ca2+ influx in histamine H1 receptor-expressing PC3 cells (Kb=47 nM). YM-344484 also inhibited the CCL11-induced chemotaxis of human CCR3-expressing cells (IC50=6.2 nM) and CCL11-induced eosinophil-derived neurotoxin release from human eosinophils (IC50=19 nM). Orally administered YM-344484 inhibited the increase in histamine-induced vascular permeability in mice (82% inhibition at a dose of 10 mg/kg) and the accumulation of eosinophils in a mouse asthma model (74% at a dose of 300 mg/kg). These results indicate that YM-344484, a novel and functional dual antagonist for chemokine CCR3 receptor and histamine H1 receptor, is an attractive candidate for development as a novel anti-allergic inflammation drug.

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