Hypothalamic neuronal histamine mediates the thyrotropin-releasing hormone-induced suppression of food intake.

Hypothalamic neuronal histamine mediates the thyrotropin-releasing hormone-induced suppression of food intake.
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下丘脑神经元组胺介导了甲状腺蛋白释放激素诱导的食物摄入抑制。

DOI:
10.1111/j.1471-4159.2007.04802.x
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发表时间:
2007-11
影响因子:
4.7
通讯作者:
Yoshimatsu, Hironobu
Yoshimatsu, Hironobu
中科院分区:
医学2区
文献类型:
--
作者:
Gotoh, Koro;Fukagawa, Koji;Fukagawa, Tomiyo;Noguchi, Hitoshi;Kakuma, Tetsuya;Sakata, Toshiie;Yoshimatsu, Hironobu

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我们研究了促甲状腺激素释放激素(TRH)和TRH 1型和2型受体(TRH-R1和TRH-R2,分别)的参与下丘脑神经元组胺的调节。与输注磷酸盐缓冲盐水的对照组相比,将100 nmol TRH输注到大鼠第三脑室(3VT)中显著降低了摄食量(p < 0.05)。在用α-氟甲基组氨酸(一种组氨酸脱羧酶的特异性自杀抑制剂)预处理的组胺耗竭大鼠和靶向破坏组胺H1受体的小鼠中,TRH诱导的摄食抑制部分减弱。在大鼠结节乳头核(TMN)、室旁核和下丘脑腹内侧核中,通过帕吉林诱导的远甲基组胺(t-MH,脑中神经元组胺的主要代谢产物)的积累,将TRH输注到3VT中增加组胺周转。此外,TRH引起的摄食量减少和组胺周转增加呈剂量依赖性。TMN内微量输注TRH可增加TMN内t-MH含量、组氨酸脱羧酶(HDC)活性和HDC mRNA表达。免疫组织化学分析显示,TRH-R2,而不是TRH-R1,在大鼠TMN的组胺能神经元的细胞体内表达。这些结果表明,下丘脑神经元组胺介导TRH诱导的摄食行为的抑制。
We examined the involvement of thyrotropin-releasing hormone (TRH) and TRH type 1 and 2 receptors (TRH-R1 and TRH-R2, respectively) in the regulation of hypothalamic neuronal histamine. Infusion of 100 nmol TRH into the rat third cerebroventricle (3vt) significantly decreased food intake (p < 0.05) compared to controls infused with phosphate- buffered saline. This TRH-induced suppression of food intake was attenuated partially in histamine-depleted rats pre-treated with α-fluoromethylhistidine (a specific suicide inhibitor of histidine decarboxylase) and in mice with targeted disruption of histamine H1 receptors. Infusion of TRH into the 3vt increased histamine turnover as assessed by pargyline-induced accumulation of tele-methylhistamine (t-MH, a major metabolite of neuronal histamine in the brain) in the tuberomammillary nucleus (TMN), the paraventricular nucleus, and the ventromedial hypothalamic nucleus in rats. In addition, TRH-induced decrease of food intake and increase of histamine turnover were in a dose-dependent manner. Microinfusion of TRH into the TMN increased t-MH content, histidine decarboxylase (HDC) activity and expression of HDC mRNA in the TMN. Immunohistochemical analysis revealed that TRH-R2, but not TRH-R1, was expressed within the cell bodies of histaminergic neurons in the TMN of rats. These results indicate that hypothalamic neuronal histamine mediates the TRH-induced suppression of feeding behavior.
DOI: 10.1073/pnas.93.23.13316
发表时间: 1996-11-12
影响因子: 11.1
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影响因子: 4.7
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