Martínez V, Rivier J, Taché Y
CURE: Digestive Diseases Research Center, West Los Angeles Veterans Administration Medical Center, Department of Medicine, Digestive Disease Division, Los Angeles, CA, USA.
J Pharmacol Exp Ther. 1999 Aug;290(2):629-34.
The effect of the corticotropin-releasing factor (CRF) receptor antagonists astressin and D-Phe CRF(12-41) injected i.v. on CRF-induced delayed gastric emptying (GE) was investigated in conscious rats. Gastric transit was assessed by the recovery of methyl cellulose/phenol red solution 20 min after its intragastric administration. The 55% inhibition of GE induced by CRF (0.6 microgram i.v.) was antagonized by 87 and 100% by i.v. astressin at 3 and 10 microgram, respectively, and by 68 and 64% by i.v. D-Phe CRF(12-41) at 10 and 20 microgram, respectively. CRF (0.6 microgram)-injected intracisternally (i.c.) induced 68% reduction of GE was not modified by i.v. astressin (10 microgram) whereas i.c. astressin (3 or 10 microgram) blocked by 58 and 100%, respectively, i.v. CRF inhibitory action. Abdominal surgery with cecal manipulation reduced GE to 7.1 +/- 3.1 and 27.5 +/- 3.3% at 30 and 180 min postsurgery, respectively, compared with 40.3 +/- 4.3 and 59.5 +/- 2.9% at similar times after anesthesia alone. Astressin (3 microgram i.v.) completely and D-Phe CRF(12-41) (20 microgram i.v.) partially (60%) blocked surgery-induced gastric stasis observed at 30 or 180 min. The CRF antagonists alone (i.v. or i.c.) had no effect on basal GE. These data indicate that CRF acts in the brain and periphery to inhibit GE through receptor-mediated interaction and that peripheral CRF is involved in acute postoperative gastric ileus; astressin is a potent peripheral antagonist of CRF when injected i.v. whereas i.c. doses >/=3 microgram exert dual central and peripheral blockade of CRF action on gastric transit.
在清醒大鼠中研究了静脉注射促肾上腺皮质激素释放因子（CRF）受体拮抗剂阿斯特辛和D - Phe CRF(12 - 41)对CRF诱导的胃排空延迟（GE）的影响。通过在胃内给予甲基纤维素/酚红溶液20分钟后回收该溶液来评估胃转运。CRF（静脉注射0.6微克）诱导的GE抑制55%，分别被静脉注射3微克和10微克的阿斯特辛拮抗87%和100%，被静脉注射10微克和20微克的D - Phe CRF(12 - 41)分别拮抗68%和64%。脑池内注射（i.c.）CRF（0.6微克）诱导GE降低68%，静脉注射阿斯特辛（10微克）对此无影响，而脑池内注射阿斯特辛（3微克或10微克）分别阻断静脉注射CRF抑制作用的58%和100%。与仅麻醉后相似时间的40.3±4.3%和59.5±2.9%相比，盲肠操作的腹部手术在术后30分钟和180分钟分别将GE降低至7.1±3.1%和27.5±3.3%。阿斯特辛（静脉注射3微克）完全阻断，D - Phe CRF(12 - 41)（静脉注射20微克）部分（60%）阻断在30分钟或180分钟观察到的手术诱导的胃淤滞。单独的CRF拮抗剂（静脉注射或脑池内注射）对基础GE无影响。这些数据表明，CRF通过受体介导的相互作用在脑和外周发挥作用以抑制GE，并且外周CRF参与急性术后胃麻痹；静脉注射时阿斯特辛是CRF的有效外周拮抗剂，而脑池内注射剂量≥3微克对CRF对胃转运的作用发挥中枢和外周双重阻断作用。
