Electrophysiological test of an amphiphilic beta-structure in LHRH action.
Electrophysiological test of an amphiphilic beta-structure in LHRH action.
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LHRH 作用中两亲性 β 结构的电生理学测试。
DOI：
10.1016/0303-7207(86)90038-9
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发表时间：
1986
影响因子：
4.1
通讯作者：
Pfaff,DW
中科院分区：
文献类型：
--
作者：
Pan,JT;Kow,LM;Kendall,DA;Kaiser,ET;Pfaff,DW
用微量移液器记录下丘脑组织切片、下丘脑弓状核（ARC）、室周核和视交叉上视前核（POA）中单个神经元的电活动。在体外应用促黄体激素释放激素（LHRH）和两种类似物（LHRH模型1和3）后测量反应。模型1（pyroGlu-His-Trp-Ser-Phe-Thr-Ile-Lys-Ile-ThrNH 2）在残基5-10中具有氨基酸取代，其被设计为形成两亲性β链结构。模型3（pyroGlu-His-Trp-Ser-Phe-Gly-Ile-Lys-Pro-SerNH 2）也被设计为具有两亲性特征，但也更接近于天然肽。电记录结果表明，LHRH对下丘脑不同的神经元既有兴奋作用，也有抑制作用，且在视前区的作用强于弓状核。对LHRH模型3的反应与对LHRH的反应密切相关，在它们的发生和方向上，对于所研究的两个大脑区域。此外，LHRH模型1和3也保留了LHRH对去甲肾上腺素和5-羟色胺的细胞反应的神经调节作用。因此，当在中枢神经系统中进行电生理学测试时，被设计为具有两亲性β结构的LHRH类似物保留了LHRH的一些性质。
Micropipettes were used to record electrical activity from single neurons in hypothalamic tissue slices, in the hypothalamic arcuate nucleus (ARC), and in the periventricular and suprachiasmatic preoptic nuclei (POA). Responses were measured following in vitro application of luteinizing hormone releasing hormone (LHRH), and two analogues: LHRH models 1 and 3. Model 1 (pyroGlu-His-Trp-Ser-Phe-Thr-Ile-Lys-Ile-ThrNH2) had amino acid substitutions in residues 5–10 designed to form an amphiphilic β-strand structure. Model 3 (pyroGlu-His-Trp-Ser-Phe-Gly-Ile-Lys-Pro-SerNH2) was also designed to possess amphiphilic characteristics, but also more closely to resemble the native peptide. Electrical recording results showed that LHRH was able both to excite or inhibit different hypothalamic neurons, and that it was more effective in the preoptic area than in the arcuate nucleus. Responses to LHRH model 3 were strongly correlated with responses to LHRH, in their occurrence and their direction, for both of the brain regions studied. Moreover, LHRH models 1 and 3 also retained the neuromodulatory effects of LHRH on cellular responses to norepinephrine and serotonin. Thus, LHRH analogues, designed to possess an amphiphilic β-structure, preserved some of the properties of LHRH when tested electrophysiologically in the central nervous system.