Impact of disrupting adenosine A₃ receptors (A₃⁻/⁻ AR) on colonic motility or progression of colitis in the mouse.
Impact of disrupting adenosine A₃ receptors (A₃⁻/⁻ AR) on colonic motility or progression of colitis in the mouse.
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DOI：
10.1002/ibd.21553
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发表时间：
2011-08
影响因子：
4.9
通讯作者：
Christofi, Fievos L.
中科院分区：
文献类型：
--
作者：
Ren, Tianhua;Grants, Iveta;Alhaj, Mazin;McKiernan, Matt;Jacobson, Marlene;Hassanain, Hamdy H.;Frankel, Wendy;Wunderlich, Jacqueline;Christofi, Fievos L.
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药理学研究表明腺苷A3AR影响运动和结肠炎。目的：使用功能性A3−/−AR敲除小鼠来证明A3AR激活是否参与调节运动或结肠炎。采用PCR基因分型、western blot和免疫化学检测A3AR。通过人工排珠、大便频率和fitc -葡聚糖转运来评估动物体内运动能力。DSS在A3−/−AR或野生型（WT）年龄、性别匹配的对照组中诱导结肠炎。通过组织病理学、MPO变化、结肠长度、CD4+细胞、体重减轻、腹泻和愈创木试验来评估结肠炎的进展。山羊抗hu- a3抗血清在结肠中鉴定出66kDa的免疫原性条带。a3ar免疫反应性在SYN+-神经曲张、s-100+-胶质细胞和隐窝细胞中表达，但在5-HT+ (EC)、CD4+ (T)、胰蛋白酶+ (MC)或肌肉细胞中不表达。结肠远端比结肠近端肌肠神经节a3ar免疫反应性为2:1。与WT相比，A3−/−AR小鼠肠道转运和脑珠排出加速；大便潴留降低了40%-60%，大便频率降低了67%。DSS下调上皮细胞中的A3AR。DSS组织病理学评分显示A3 - / - AR小鼠的粘膜损伤比WT小。A3 - / - AR表型可防止DSS引起的体重减轻、中性粒细胞（MPO）或CD4+-T细胞浸润、结肠缩短、脾重改变、腹泻或隐血。A3−/−AR小鼠的A3AR功能破坏可改变肠道运动。我们假设腺苷的持续释放和突触前抑制A3AR的激活可以减缓转运并抑制排便反射。A3AR可能参与胶质传递。在单独的研究中，A3 - / - AR可以预防dss -结肠炎，这与A3AR激活有助于结肠炎发展的新假设一致。
Pharmacological studies suggest adenosine A3AR influences motility and colitis. Aim: Functional A3−/−AR knockout mice were used to prove whether A3AR activation is involved in modulating either motility or colitis. A3AR was probed by PCR genotyping, western blot and immunochemistry. Motility was assessed in vivo by artificial bead-expulsion, stool-frequency and FITC-Dextran transit. Colitis was induced with DSS in A3−/−AR or wild-type (WT) age, sex-matched-controls. Progression of colitis was evaluated by histopathology, changes in MPO, colon length, CD4+-cells, weight-loss, diarrhea and the Guaiac-test. Goat anti-hu-A3 antiserum identified a 66kDa immunogenic-band in colon. A3AR-immunoreactivity is expressed in SYN+-nerve varicosities, s-100+-glia and crypt cells, but not 5-HT+ (EC), CD4+ (T), tryptase+ (MC) or muscle cells. A3AR-immunoreactivity in myenteric ganglia of distal colon ≫ proximal colon by a ratio of 2:1. Intestinal transit and bead expulsion were accelerated in A3−/−AR mice compared to WT; stool retention was lower by 40%–60% and stool frequency by 67%. DSS down-regulated A3AR in epithelia. DSS histopathology scores indicated less mucosal damage in A3−/−AR mice than WT. A3−/−AR phenotype protected against DSS-induced weight-loss, neutrophil (MPO) or CD4+-T cell infiltration, colon shortening, change in splenic weight, diarrhea or occult-fecal blood. Functional disruption of A3AR in A3−/−AR mice alters intestinal motility. We postulate that ongoing release of adenosine and activation of presynaptic-inhibitory A3AR can slow down transit and inhibit the defecation reflex. A3AR may be involved in gliotransmission. In separate studies, A3−/−AR protects against DSS-colitis consistent with a novel hypothesis that A3AR activation contributes to development of colitis.
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影响因子：
3.1
作者：
Cavalcante, IC;Castro, MV;Brito, GAC
通讯作者：
Brito, GAC
DOI：
10.1152/ajpgi.1999.276.4.g875
发表时间：
1999-04-01
影响因子：
4.5
作者：
Deshpande, NA;McDonald, TJ;Cook, MA
通讯作者：
Cook, MA
影响因子：
29.4
作者：
Christofi, FL;Kim, M;Cooke, HJ
通讯作者：
Cooke, HJ
影响因子：
29.4
作者：
Castaneda, FE;Walia, B;Sitaraman, SV
通讯作者：
Sitaraman, SV
影响因子：
--
作者：
CRONSTEIN, BN;NAIME, D;FIRESTEIN, G
通讯作者：
FIRESTEIN, G