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脑池内尿皮质素抑制大鼠迷走神经刺激引起的胃动力:促肾上腺皮质激素释放因子(2)的作用

Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: role of CRF(2).

作者信息

Chen C-Y, Million M, Adelson D W, Martínez V, Rivier J, Taché Y

机构信息

CURE: Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, California 90073, USA.

出版信息

Br J Pharmacol. 2002 May;136(2):237-47. doi: 10.1038/sj.bjp.0704713.

Abstract
  1. Corticotropin-releasing factor (CRF) acts in the brain to inhibit thyrotropin-releasing hormone (TRH) analogue, RX-77368-induced vagal stimulation of gastric motility. We investigated CRF receptor-mediated actions of rat urocortin (rUcn) injected intracisternally (ic) on gastric motor function. 2. Urethane-anaesthetized rats with strain gauges on the gastric corpus were injected i.c. with rUcn and 20 min later, with i.c. RX-77368. CRF antagonists were injected i.c. 10 min before rUcn. 3. RX-77368 (1.5, 3, 10, 30 and 100 ng, i.c.) dose-dependently increased corpus contractions, expressed as total area under the curve (AUC, mV min(-1)) to 2.6+/-2.5, 6.1+/-5.9, 9.8+/-2.6, 69.7+/-21.7 and 74.9+/-28.7 respectively vs 0.2+/-0.1 after i.c. saline. Ucn (1, 3 or 10 microg) inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93% respectively vs i.c. saline+RX-77368. 4. The CRF(1)/CRF(2) antagonist, astressin-B (60 microg, i.c.) completely blocked i.c. rUcn (3 microg, i.c.)-induced inhibition of gastric motility stimulated by RX-77368 (30 ng). 5. The selective CRF(2) antagonist, astressin(2)-B (30, 60 or 100 microg, i.c. ) dose-dependently prevented i.c. rUCn action while the CRF(1) antagonist, NBI-27914 did not. 6. In conscious rats, rUcn (0.6 or 1 microg, i.c.) inhibited gastric emptying of an ingested chow meal by 61 and 92% respectively. rUcn action was antagonized by astressin(2)-B. 7. These data show that i.c. rUcn acts through CRF(2) receptors to inhibit central vagal gastric contractile response and postoprandial emptying.
摘要
  1. 促肾上腺皮质激素释放因子(CRF)在大脑中发挥作用,抑制促甲状腺激素释放激素(TRH)类似物RX - 77368诱导的迷走神经对胃动力的刺激。我们研究了脑池内注射大鼠尿皮质素(rUcn)对胃运动功能的CRF受体介导作用。2. 用应变片置于胃体的氨基甲酸乙酯麻醉大鼠,脑池内注射rUcn,20分钟后,再脑池内注射RX - 77368。在注射rUcn前10分钟脑池内注射CRF拮抗剂。3. RX - 77368(1.5、3、10、30和100 ng,脑池内注射)剂量依赖性地增加胃体收缩,以曲线下总面积(AUC,mV min⁻¹)表示,分别为2.6±2.5、6.1±5.9、9.8±2.6、69.7±21.7和74.9±28.7,而脑池内注射生理盐水后为0.2±0.1。Ucn(1、3或10 μg)分别使RX - 77368(30 ng)诱导的总AUC增加量比脑池内注射生理盐水+RX - 77368时降低28%、62%和93%。4. CRF(1)/CRF(2)拮抗剂阿斯特辛 - B(60 μg,脑池内注射)完全阻断了脑池内注射rUcn(3 μg,脑池内注射)对RX - 77368(30 ng)刺激的胃动力的抑制作用。5. 选择性CRF(2)拮抗剂阿斯特辛(2)-B(30、60或100 μg,脑池内注射)剂量依赖性地阻止脑池内注射rUcn的作用,而CRF(1)拮抗剂NBI - 27914则无此作用。6. 在清醒大鼠中,rUcn(0.6或1 μg,脑池内注射)分别使摄入的食物餐胃排空抑制61%和92%。rUcn的作用被阿斯特辛(2)-B拮抗。7. 这些数据表明,脑池内注射rUcn通过CRF(2)受体发挥作用,抑制中枢迷走神经对胃的收缩反应和餐后排空。

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