Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by α2-adrenoceptors in the presence of experimental colitis
Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by α2-adrenoceptors in the presence of experimental colitis
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DOI：
10.1038/sj.bjp.0705249
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发表时间：
2003-05-01
影响因子：
7.3
通讯作者：
Del Tacca, M
中科院分区：
文献类型：
--
作者：
Blandizzi, C;Fornai, M;Del Tacca, M
1本研究探讨肠道炎症对以下两个方面的影响：(1)α(2)-肾上腺素能受体对肠道神经传递和运动的调控；(2)肠道α(2)-肾上腺素能受体的表达。用2，4-二硝基苯磺酸(DNBS)直肠注射诱导大鼠实验性结肠炎。2 UK-14,304抑制阿托品敏感的回肠和结肠纵肌的电诱发收缩。UK-14,304对DNBS治疗动物的组织具有类似的效力，但更有效；其作用可被酚妥拉明比柔红素更有效地拮抗。3在结肠炎存在的情况下，电诱导的[H-3]去甲肾上腺素从回肠制剂中释放减少。UK-14,304可减少氚流出，并被肉豆蔻碱或酚妥拉明刺激：这些作用在结肠炎动物的制剂中得到增强。4逆转录-聚合酶链式反应和Western印迹分析表明，从回肠和结肠分离的粘膜和肌肉组织中α(2A)-肾上腺素能受体的蛋白表达。结肠炎的诱导增加了回肠和结肠肌层的α(2A)-肾上腺素受体的表达，但没有伴随粘膜组织的变化。5在体内，诱导结肠炎降低了木炭混悬液的胃肠推进。在这种情况下，胃肠传输被抑制的腹膜(Ip)。UK-14,304，由ip刺激。Ruwolscine。乙双胺预处理后，肉毒碱的兴奋作用不再存在，UK-14,304发挥了更显著的抑制作用，但被肉毒碱所拮抗。6本研究结果表明，在肠炎症存在的情况下，突触前α(2)-肾上腺素受体有助于增强对炎症和非炎症远端部位胆碱能和去甲肾上腺素能传递的抑制控制。有证据表明，这种调节作用依赖于肠道神经系统内α(2A)肾上腺素受体表达的增加。
1 This study investigates the influence of intestinal inflammation on: (1) the control of intestinal neurotransmission and motility by prejunctional alpha(2)-adrenoceptors and (2) the expression of intestinal alpha(2)-adrenoceptors. Experimental colitis was induced by intrarectal administration of 2,4-dinitrobenzenesulphonic acid (DNBS) to rats.2 UK-14,304 inhibited atropine-sensitive electrically evoked contractions of ileal and colonic longitudinal muscle preparations. UK-14,304 acted with similar potency, but higher efficacy, on tissues from DNBS-treated animals; its effects were antagonized with greater potency by phentolamine than rauwolscine.3 Electrically induced [H-3] noradrenaline release from ileal preparations was reduced in the presence of colitis. Tritium outflow was decreased by UK-14,304 and stimulated by rauwolscine or phentolamine: these effects were enhanced in preparations from animals with colitis.4 Reverse transcription-polymerase chain reaction and Western blot assay demonstrated the protein expression of alpha(2A)-adrenoceptors in mucosal and muscular tissues isolated from ileum and colon. The induction of colitis increased alpha(2A)-adrenoceptor expression in both ileal and colonic muscular layers, without concomitant changes in mucosal tissues.5 Induction of colitis reduced gastrointestinal propulsion of a charcoal suspension in vivo. In this setting, the gastrointestinal transit was inhibited by intraperitoneal (i.p.) UK-14,304 and stimulated by i.p. rauwolscine. After pretreatment with guanethidine, the stimulant action of rauwolscine no longer occurred, and UK-14,304 exerted a more prominent inhibitory effect that was antagonized by rauwolscine.6 The present results indicate that, in the presence of intestinal inflammation, prejunctional alpha(2)-adrenoceptors contribute to an enhanced inhibitory control of cholinergic and noradrenergic transmission both at inflamed and noninflamed distant sites. Evidence was obtained that such modulatory actions depend on an increased expression of alpha(2A)-adrenoceptors within the enteric nervous system.