Martínez V, Taché Y
CURE: Digestive Diseases Research Center, Veterans Administration Greater Los Angeles Healthcare System, Department of Medicine, Digestive Disease Division and Brain Research Institute, University of California at Los Angeles, Los Angeles, CA 90073,USA.
Brain Res. 2001 Mar 2;893(1-2):29-35. doi: 10.1016/s0006-8993(00)03277-7.
The CRF receptor subtype mediating the colonic and gastric motor responses to central CRF was investigated in conscious rats. CRF (0.6 microg/rat) injected intracerebroventicularly (i.c.v.) or 1 h water avoidance stress stimulated defecation (pellet/60 min: 4.1+/-1.0 and 8.7+/-0.7 respectively vs. 0.3+/-0.3 in i.c.v. vehicle/no stress). The CRF receptor 1 (CRF-R1) antagonist, NBI-27914 (50-100 microg/rat) injected i.c.v., abolished the colonic response to i.c.v. CRF and dose-dependently reduced that induced by water avoidance stress. NBI-27914 (100 microg/rat) injected peripherally did not influence the defecatory response to stress. The peptide CRF-R1/R2 antagonist, astressin (10 microg/rat, i.c.v.) inhibited the colonic motor response to i.c.v. CRF and stress similarly as NBI-27914 injected i.c.v. at 100 microg/rat. Intracisternal (i.c.) injection of astressin (10 microg/rat) also completely prevented CRF (0.6 g, i.c.)-induced delayed gastric emptying while i.c. NBI-27914 (50 or 100 microg) had no effect. These results indicate a differential role of central CRF receptor subtypes in the colonic stimulatory and gastric inhibitory motor responses to central CRF and that the CRF component of stress-related activation of colonic expulsion is primarily mediated by CRF-R1.
在清醒大鼠中研究了介导结肠和胃对中枢促肾上腺皮质激素释放因子（CRF）运动反应的CRF受体亚型。脑室内注射（i.c.v.）CRF（0.6微克/只大鼠）或1小时的禁水应激刺激排便（每60分钟粪便数：分别为4.1±1.0和8.7±0.7，而i.c.v.注射溶媒/无应激组为0.3±0.3）。脑室内注射CRF受体1（CRF-R1）拮抗剂NBI-27914（50-100微克/只大鼠）可消除结肠对i.c.v. CRF的反应，并剂量依赖性地降低禁水应激诱导的反应。外周注射NBI-27914（100微克/只大鼠）不影响对应激的排便反应。肽类CRF-R1/R2拮抗剂astressin（10微克/只大鼠，i.c.v.）抑制结肠对i.c.v. CRF和应激的运动反应，其作用与100微克/只大鼠脑室内注射NBI-27914相似。脑池内（i.c.）注射astressin（10微克/只大鼠）也完全阻止了CRF（0.6微克，i.c.）诱导的胃排空延迟，而脑池内注射NBI-27914（50或100微克）则无此作用。这些结果表明，中枢CRF受体亚型在结肠刺激和胃抑制对中枢CRF的运动反应中具有不同作用，且应激相关的结肠排出激活中的CRF成分主要由CRF-R1介导。
