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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Hypothalamic paraventricular 5-hydroxytryptamine inhibits the effects of ghrelin on eating and energy substrate utilization.
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Hypothalamic paraventricular 5-hydroxytryptamine inhibits the effects of ghrelin on eating and energy substrate utilization.

机译：下丘脑室旁5-羟色胺抑制生长激素释放肽对饮食和能量底物利用的影响。

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摘要

Ghrelin microinjections into discrete regions of the hypothalamus, including the paraventricular nucleus (PVN), stimulate eating and promote carbohydrate oxidation, effects similar to PVN microinjection of neuropeptide Y (NPY). We have also reported that NPY's orexigenic and metabolic effects are antagonized by pretreatment with 5-hydroxytryptamine (5-HT) or 5-HT receptor agonists. In order to determine whether 5-HT also inhibits ghrelin's orexigenic and metabolic actions, the present study examined the effects of 5-HT pretreatment on ghrelin-induced alterations in eating and energy substrate utilization following direct injections into the hypothalamic PVN. Both 5-HT (5-20 nmol) and ghrelin (100 pmol) were administered at the onset of the dark cycle. Food intake was measured 2h postinjection. A separate group of rats (n=8) was injected with 5-HT paired with ghrelin and respiratory quotient (RQ; VCO(2)/VO(2)) was measured over 2h using an open circuit calorimeter. PVN injections of ghrelin increased food intake and increased RQ, reflecting a shift in energy substrate utilization in favor of carbohydrate oxidation. 5-HT effectively blocked the effects of ghrelin on both food intake and RQ. We then administered the 5-HT(2A/2C), receptor agonist, DOI, immediately prior to ghrelin. Similar to 5-HT, PVN DOI blocked ghrelin-induced eating and inhibited the peptide's effect on substrate utilization. These data are in agreement with other evidence suggesting that ghrelin functions as a gut-brain peptide in the control of food intake and energy metabolism, and indicate that 5-HT acts within the PVN to modulate ghrelin's orexigenic and metabolic signaling.
机译：Ghrelin显微注射到下丘脑的离散区域，包括心室旁核（PVN），刺激进食并促进碳水化合物氧化，其作用类似于神经肽Y（NPY）的PVN显微注射。我们还报告说，用5-羟色胺（5-HT）或5-HT受体激动剂预处理可拮抗NPY的致癌和代谢作用。为了确定5-HT是否也抑制生长激素释放肽的促食欲和代谢作用，本研究检查了5-HT预处理对直接注入下丘脑PVN中的生长激素释放肽诱导的饮食和能量底物利用率变化的影响。在黑暗周期开始时同时给予5-HT（5-20​​ nmol）和生长素释放肽（100 pmol）。注射后2小时测量食物摄入量。另一组大鼠（n = 8）注射了与ghrelin配对的5-HT，并使用开路热量计在2小时内测量了呼吸商（RQ; VCO（2）/ VO（2））。 ghrelin的PVN注射增加了食物摄入并提高了RQ，这反映了能量底物利用率的变化，有利于碳水化合物的氧化。 5-HT有效地阻断了ghrelin对食物摄入和RQ的影响。然后，我们在生长素释放肽释放前立即施用了5-HT（2A / 2C）受体激动剂DOI。与5-HT相似，PVN DOI阻断了生长素释放肽诱导的进食并抑制了该肽对底物利用率的影响。这些数据与其他证据相吻合，这些证据表明ghrelin在控制食物摄入和能量代谢中起着肠脑肽的作用，并表明5-HT在PVN中起作用以调节ghrelin的致食性和代谢信号传导。

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