肽类促肾上腺皮质激素释放因子（CRF）受体拮抗剂对人/大鼠CRF行为效应的影响。

Influence of peptide CRF receptor antagonists upon the behavioural effects of human/rat CRF.

作者信息

Jones D N, Kortekaas R, Hatcher P D, Middlemiss D N, White A, Hagan J J

机构信息

Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.

出版信息

Eur J Pharmacol. 1999 Jun 4;373(2-3):141-5. doi: 10.1016/s0014-2999(99)00287-3.

DOI:10.1016/s0014-2999(99)00287-3

PMID:10414432

Abstract

The effects of the corticotropin-releasing factor (CRF) receptor antagonists, alpha-helical CRF-(9-41), [D-Phe12,Nle21,38, CalphaMe-Leu37]humanCRF-(12-41) (D-PheCRF-(12-41)) and astressin ([cyclo(30-33)[D-Phe12,Nle21,38,Glu30,Lys33]h umanCRF-(12-41) upon hypophagic and motor activation response to human/ratCRF (h/rCRF) were investigated. All three antagonists (100 microg intracerebroventricular (i.c.v.)) blocked the effects of h/rCRF (1 microg i.c.v.) upon food intake and body weight change in food-deprived rats. In contrast, alpha-helical CRF-(9-41) and astressin (both at 100 microg i.c.v., but not lower doses), but not D-PheCRF-(12-41) (up to 100 microg i.c.v.), blocked h/rCRF (0.3 microg i.c.v.)-induced motor activation in rats in a familiar environment. The ability of D-PheCRF-(12-41) to block CRF-induced hypophagia, but not motor activation, suggests a selective action of this antagonist upon the behavioural effects of centrally administered h/rCRF.

摘要

研究了促肾上腺皮质激素释放因子（CRF）受体拮抗剂α-螺旋CRF-（9 - 41）、[D-苯丙氨酸12，Nle21,38，α-甲基亮氨酸37]人CRF-（12 - 41）（D-PheCRF-（12 - 41））和阿斯特辛（[环（30 - 33）[D-苯丙氨酸12，Nle21,38，谷氨酸30，赖氨酸33]人CRF-（12 - 41）]对饥饿大鼠进食和运动激活反应的影响。所有三种拮抗剂（脑室内注射100微克）均能阻断人/大鼠CRF（h/rCRF，脑室内注射1微克）对饥饿大鼠食物摄入量和体重变化的影响。相比之下，α-螺旋CRF-（9 - 41）和阿斯特辛（均为脑室内注射100微克，但较低剂量无效），而非D-PheCRF-（12 - 41）（脑室内注射剂量高达100微克），能阻断在熟悉环境中h/rCRF（脑室内注射0.3微克）诱导的大鼠运动激活。D-PheCRF-（12 - 41）能够阻断CRF诱导的摄食减少，但不能阻断运动激活，这表明该拮抗剂对中枢给予的h/rCRF的行为效应具有选择性作用。