Involvement of peripheral alpha2A adrenoceptor in the acceleration of gastrointestinal transit and abdominal visceral pain induced by intermittent deprivation of REM sleep.
Involvement of peripheral alpha2A adrenoceptor in the acceleration of gastrointestinal transit and abdominal visceral pain induced by intermittent deprivation of REM sleep.
复制标题
外周 α2A 肾上腺素受体参与胃肠道运输加速和间歇性快速眼动睡眠剥夺引起的腹部内脏疼痛。
DOI：
10.1016/j.physbeh.2018.01.010
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Tan-No K.
中科院分区：
文献类型：
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作者：
Yaoita F;Muto M;Murakami H;Endo S;Kozawa M;Tsuchiya M;Tadano T;Tan-No K.
许多研究将睡眠改变与肠易激综合征（IBS）症状的严重程度联系起来，但直接的病理生理关系尚未阐明。此外，去甲肾上腺素能信号传导的改变与IBS的病理生理学有关，α 2-肾上腺素受体是潜在的治疗靶点。我们先前已经表明，间歇性快速眼动（REM）睡眠剥夺应激引起的胃肠运输（GIT）加速可能符合IBS模型的特征。此外，我们还发现了睡眠剥夺小鼠大脑中的高去甲肾上腺素能功能。另一方面，醋酸引起的扭体反应表明IBS模型动物的内脏疼痛特征。在这项研究中，使用小鼠，我们调查了间歇性REM睡眠剥夺应激是否会导致乙酸诱导的扭体反应的变化，以及是否通过给予亲水性可乐定类似物ST-91来改善扭体反应和GIT的数量。使用小平台方法（20小时/天）间歇性剥夺小鼠REM睡眠3天。间歇性REM睡眠剥夺应激引起GIT加速，ST-91治疗显著改善了扭体次数的增加。ST-91对笼内对照小鼠和间歇性REM睡眠剥夺小鼠GIT的ID 50值分别为0.24和0.70 mg/kg。此外，ST-91对笼内对照小鼠和间歇性REM睡眠剥夺小鼠扭体的ID 50值分别为0.52和0.73 mg/kg。此外，α 2A-肾上腺素能受体的表达减少，在远端回肠的间歇性REM睡眠剥夺小鼠相比，在笼子里控制的小鼠。此外，ST-91对笼内对照和间歇REM睡眠剥夺小鼠的GIT和扭体的作用通过施用BRL 44408（6mg/kg，i.p.）而降低，选择性α 2A-肾上腺素受体拮抗剂，而不是通过给予丙咯生（3mg/kg，i.p.），或JP-1302（3mg/kg，i.p.），分别为选择性α 2B-和α 2C-肾上腺素受体拮抗剂。这些结果表明，间歇性REM睡眠剥夺应激引起的GIT和扭体反应的增加可以作为IBS腹泻和内脏疼痛症状的模型。此外，这些症状的发作可能与外周α 2A-肾上腺素受体功能低下有关。
Many studies have associated sleep alterations with the severity of irritable bowel syndrome (IBS) symptoms, but the direct pathophysiological relationship has not been clarified. In addition, alterations in noradrenergic signaling have been implicated in the pathophysiology of IBS, and alpha2-adrenoceptors are potential treatment targets. We have previously shown that acceleration of gastrointestinal transit (GIT) elicited by intermittent rapid eye movement (REM) sleep deprivation stress may fulfill the profile of a model of IBS. Moreover, we showed hypernoradrenergic function in the brain of sleep-deprived mice. On the other hand, acetic acid-induced writhes indicate visceral pain features of IBS model animals. In this study, using mice, we investigated whether intermittent REM sleep deprivation stress causes changes in acetic acid-induced writhing and whether the number of writhes and GIT are improved by administration of the hydrophilic clonidine analogue, ST-91. Mice were deprived of REM sleep intermittently using the small-platform method (20 h/day) for 3 days. The intermittent REM sleep deprivation stress elicited acceleration of GIT and the increased number of writhes was significantly improved by ST-91 treatment. The ID50 values of ST-91 on the GIT in cage-control mice and intermittent REM sleep-deprived mice were 0.24 and 0.70 mg/kg, respectively. In addition, the ID50 values of ST-91 on the writhes in cage-control mice and intermittent REM sleep-deprived mice were 0.52 and 0.73 mg/kg, respectively. Further, the expression of alpha2A-adrenoceptor was decreased in the distal ileum of intermittent REM sleep-deprived mice compared to that in cage-control mice. Moreover, the effects of ST-91 on GIT and writhes in cage-control and intermittent REM sleep-deprived mice were decreased by the administration of BRL44408 (6 mg/kg, i.p.), a selective alpha2A–adrenoceptor antagonist, and not by the administration of imiloxan (3 mg/kg, i.p.), or JP-1302 (3 mg/kg, i.p.), selective alpha2B-and alpha2C–adrenoceptor antagonists, respectively. These results suggest that the increase in GIT and writhes induced by intermittent REM sleep deprivation stress may serve as a model of diarrhea and visceral pain symptoms in IBS. Further, the onset of these symptoms may be related to the hypofunction of peripheral alpha2A–adrenoceptor.