Haas D A, Sturtridge W C, George S R
Department of Medicine, University of Toronto, Ontario, Canada.
Neuroscience. 1990;38(3):693-701. doi: 10.1016/0306-4522(90)90063-a.
There is presently no consensus as to the nature of the catecholaminergic influence on the regulation of corticotropin-releasing factor. The potential role that the alpha-adrenergic system plays was investigated by measuring hypothalamic corticotropin-releasing factor-like immunoreactivity and plasma adrenocorticotropin, following manipulation of alpha-1 and alpha-2 adrenergic receptor activation. Administration of the alpha-1 agonist methoxamine did not significantly alter either plasma adrenocorticotropin or hypothalamic corticotropin-releasing factor. Administration of the alpha-2 agonist clonidine resulted in a 24-fold increase in plasma adrenocorticotropin and a significant decrease in median eminence corticotropin-releasing factor, consistent with its release. Corticotropin-releasing factor in the remainder of the hypothalamus was not altered. Concurrent administration of clonidine with the selective alpha-2 antagonist yohimbine prevented the clonidine-induced changes in plasma adrenocorticotropin and hypothalamic corticotropin-releasing factor, consistent with the clonidine effect being mediated through alpha-2 receptors. Concurrent administration of clonidine with methoxamine did not prevent these effects, suggesting that the effect of clonidine was not mediated through presynaptic inhibition of noradrenergic adrenergic neurotransmission. Inhibition of protein synthesis by anisomycin induced changes in corticotropin-releasing factor and adrenocorticotropin which were not altered by combined treatment with methoxamine or clonidine. These data suggest differential roles for alpha-1 and alpha-2 systems in the regulation of corticotropin-releasing factor. Results from alpha-2 adrenergic activation were consistent with stimulation of corticotropin-releasing factor release, an effect mediated by a postsynaptic alpha-2 mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
目前，关于儿茶酚胺能对促肾上腺皮质激素释放因子调节的影响的本质尚无共识。通过测量α-1和α-2肾上腺素能受体激活被操控后的下丘脑促肾上腺皮质激素释放因子样免疫反应性和血浆促肾上腺皮质激素，研究了α-肾上腺素能系统所起的潜在作用。给予α-1激动剂甲氧明并未显著改变血浆促肾上腺皮质激素或下丘脑促肾上腺皮质激素释放因子。给予α-2激动剂可乐定导致血浆促肾上腺皮质激素增加24倍，且正中隆起促肾上腺皮质激素释放因子显著减少，这与其释放情况相符。下丘脑其余部分的促肾上腺皮质激素释放因子未发生改变。可乐定与选择性α-2拮抗剂育亨宾同时给药可防止可乐定诱导的血浆促肾上腺皮质激素和下丘脑促肾上腺皮质激素释放因子的变化，这表明可乐定的作用是通过α-2受体介导的。可乐定与甲氧明同时给药并未阻止这些效应，这表明可乐定的作用不是通过去甲肾上腺素能神经传递的突触前抑制介导的。茴香霉素抑制蛋白质合成诱导了促肾上腺皮质激素释放因子和促肾上腺皮质激素的变化，而甲氧明或可乐定联合治疗并未改变这些变化。这些数据表明α-1和α-2系统在促肾上腺皮质激素释放因子调节中具有不同作用。α-2肾上腺素能激活的结果与促肾上腺皮质激素释放因子释放的刺激一致，该效应由突触后α-2机制介导。（摘要截短至250字）
