A2a receptors mediate inhibitory effects of adenosine on colonic motility in the presence of experimental colitis
A2a receptors mediate inhibitory effects of adenosine on colonic motility in the presence of experimental colitis
复制标题
DOI：
10.1097/01.mib.0000198535.13822.a9
复制
发表时间：
2006-02-01
影响因子：
4.9
通讯作者：
Del Tacca, M
中科院分区：
文献类型：
--
作者：
Antonioli, L;Fornai, M;Del Tacca, M
背景：腺苷调节免疫和炎症，也可作为肠道功能的调节剂。在这项研究中，我们在实验性结肠炎大鼠模型中研究了腺苷A2a受体对结肠运动的作用。方法：通过2,4-二硝基苯磺酸诱导结肠炎。测定了 ZM 241385（A2a 受体拮抗剂）和 CGS 21680（A2a 受体激动剂）对跨壁电刺激 (TES) 或卡巴胆碱引起的结肠纵向肌肉制剂的胆碱能收缩的影响。通过逆转录聚合酶链式反应评估结肠神经肌肉层中的 A2a 受体表达。结果：在不存在或存在结肠炎的情况下，ZM 241385 增加 TES 诱导的收缩，该药物在来自发炎动物的结肠制剂中更有效。 ZM 241385 的增强作用不受胍乙啶或 α-chimotrypsin 的影响，而受到 N-omega-丙基-L-精氨酸（神经元一氧化氮合酶抑制剂）或腺苷 5'-（α,β-亚甲基）二磷酸（胞外 5'-核苷酸酶抑制剂）的影响。将正常或发炎大鼠的结肠组织暴露于双嘧达莫加腺苷脱氨酶以降低内源性腺苷水平时，CGS 21680 会引起对 TES 的收缩反应的浓度依赖性降低，这在发炎大鼠的制剂中更为强烈，并被 ZM 241385 拮抗。CGS 21680 和 ZM 241385 均不受影响卡巴胆碱引起的收缩。逆转录聚合酶链反应显示从发炎动物分离的结肠组织中 A2a 受体表达增加。结论：腺苷系统参与发炎肠道中发生的神经塑性变化。 A2a 受体通过促进抑制性氮能通路来调节结肠兴奋性胆碱能神经的活性，并且这种调节功能在肠道炎症存在时增强。
Background: Adenosine regulates immunity and inflammation, and acts also as a modulator of gut functions. In this study, we investigated the role of adenosine A2a receptors on colonic motility in a rat model of experimental colitis.Methods: Colitis was induced by 2,4-dinitrobenzenesulfonic acid. The effects of ZM 241385 (A2a receptor antagonist) and CGS 21680 (A2a receptor agonist) were assayed on cholinergic contractions of colonic longitudinal muscle preparations evoked by transmural electrical stimulation (TES) or carbachol. A2a receptor expression in colonic neuromuscular layers was assessed by reverse transcription-polymerase chain reaction.Results: ZM 241385 increased TES-induced contractions in the absence or in the presence of colitis, the drug being more effective in colonic preparations from inflamed animals. The enhancing effects of ZM 241385 were unaffected by guanethidine or alpha-chimotrypsin, whereas being prevented by N-omega-propyl-L-arginine (neuronal nitric oxide synthase inhibitor) or adenosine 5'-(alpha,beta-methylene) diphosphate (ecto-5'-nucleotidase inhibitor). Upon exposure of colonic tissues from normal or inflamed rats to dipyridamole plus adenosine deaminase, to abate endogenous adenosine levels, CGS 21680 evoked concentration-dependent reductions of contractile responses to TES, which were more intense in preparations from inflamed rats, and were antagonized by ZM 241385. Neither CGS 21680 nor ZM 241385 affected carbachol-induced contractions. Reverse transcription-polymerase chain reaction showed an increase in A2a receptor expression in colonic tissues isolated from inflamed animals.Conclusions: The adenosine system is involved in neuroplastic changes occurring in inflamed gut. A2a receptors modulate the activity of colonic excitatory cholinergic nerves via facilitatory control on inhibitory nitrergic pathways, and such a regulatory function is enhanced in the presence of bowel inflammation.