Bovetto S, Rouillard C, Richard D
Départment de Physiologie, Faculté de Médecine, Université Laval, Québec, Canada.
Am J Physiol. 1996 Nov;271(5 Pt 2):R1231-8. doi: 10.1152/ajpregu.1996.271.5.R1231.
Two series of experiments were conducted to investigate the role of corticotropin-releasing hormone (CRH) in the effects of 5-hydroxytryptamine (5-HT) on energy intake and energy expenditure. The first set of experiments was carried out to confirm the influence of 5-HT1A-, 5-HT1B-, 5-HT2A/2C-receptor agonists on the activation of the hypothalamic-pituitary-adrenal axis. Plasma corticosterone levels were measured, and a double-immunolabeling procedure was used to determine whether the neuronal activity marker, c-Fos protein (Fos), could be found within brain neurons containing CRH after treatments with 5-HT1A-, 5-HT1B-, 5-HT2A/2C-receptor agonists. The second series of experiments was conducted to assess the involvement of CRH in the effects of 5-HT on food intake and metabolic rate (VO2). The effects of the 5-HT1A-, 5-HT1B-, 5-HT2A/2C-receptor agonists on food intake and VO2 were measured in rats treated with the CRH antagonist, alpha-helical CRH-(9-41). In both experiments rats were intraperitoneally injected with either a vehicle (NaCl 0.9%), the 5-HT1A-receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT), the 5-HT1B-receptor agonist 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU-24969), or the 5-HT2A/2C-receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). Fos immunoreactivity was detectable within the CRH-containing neurons of the paraventricular nucleus of the hypothalamus (PVH) after injection of each of the 5-HT-receptor agonists used. The CRH antagonist alpha-helical CRH-(9-41) attenuated the increases in metabolic rate induced by DOI and 8-OH-DPAT. alpha-Helical CRH did not, however, prevent the effects of RU-24969 and DOI on either nocturnal metabolic rate or food intake. The present results provide further evidence for a role of CRH in 5-HT-mediated thermogenic effect, which likely involves the 5-HT2A/2C receptor during the day and the 5-HT1A receptor during the night. Moreover, these results do not support a role for CRH in 5-HT anorectic effects, which likely involves 5-HT1B and 5-HT2A/2C receptors. Finally, the results of this study indicate that the stimulation of CRH-containing neurons located in the PVH does not necessarily predict changes in food intake and energy expenditure.
进行了两组实验来研究促肾上腺皮质激素释放激素（CRH）在5-羟色胺（5-HT）对能量摄入和能量消耗影响中的作用。第一组实验旨在证实5-HT1A、5-HT1B、5-HT2A/2C受体激动剂对下丘脑-垂体-肾上腺轴激活的影响。测量血浆皮质酮水平，并采用双重免疫标记程序来确定在用5-HT1A、5-HT1B、5-HT2A/2C受体激动剂处理后，在含有CRH的脑神经元内是否能发现神经元活性标记物c-Fos蛋白（Fos）。第二组实验旨在评估CRH在5-HT对食物摄入和代谢率（VO2）影响中的作用。在用CRH拮抗剂α-螺旋CRH-（9-41）处理的大鼠中，测量5-HT1A、5-HT1B、5-HT2A/2C受体激动剂对食物摄入和VO2的影响。在两个实验中，大鼠均腹腔注射溶剂（0.9%氯化钠）、5-HT1A受体激动剂（±）-8-羟基-2-（二正丙基氨基）四氢溴化萘（8-OH-DPAT）、5-HT1B受体激动剂5-甲氧基-3-（1,2,3,6-四氢-4-吡啶基）-1H-吲哚琥珀酸盐（RU-24969）或5-HT2A/2C受体激动剂（±）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷盐酸盐（DOI）。注射每种使用的5-HT受体激动剂后，可以在下丘脑室旁核（PVH）中含有CRH的神经元内检测到Fos免疫反应性。CRH拮抗剂α-螺旋CRH-（9-41）减弱了DOI和8-OH-DPAT诱导的代谢率升高。然而，α-螺旋CRH并不能阻止RU-24969和DOI对夜间代谢率或食物摄入的影响。目前的结果为CRH在5-HT介导的产热效应中的作用提供了进一步的证据，这可能在白天涉及5-HT2A/2C受体，在夜间涉及5-HT1A受体。此外，这些结果不支持CRH在5-HT厌食效应中的作用，5-HT厌食效应可能涉及5-HT1B和
