Intracellular calcium concentrations regulated by cyclic ADP-ribose and heat in the mouse hypothalamus
Intracellular calcium concentrations regulated by cyclic ADP-ribose and heat in the mouse hypothalamus
复制标题
小鼠下丘脑中环 ADP-核糖和热量调节细胞内钙浓度
DOI：
10.1166/msr.2012.1015
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Higashida,H
中科院分区：
文献类型：
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作者：
Liu,H.-X.;Hashii,M.;Higashida,H
催产素（OT）是由下丘脑合成和释放的，在哺乳动物的社会识别和行为中起着关键作用。脑OT释放主要是由于CD 38的ADP-核糖基环化酶活性催化的环ADP-核糖（cADPR）从Ca 2+池中动员Ca 2+诱导的细胞内胞浆Ca 2+浓度（[Ca 2 +] i）升高。最近，我们报道了细胞外应用cADPR，连同热，增加[Ca 2 +] i在培养的神经元肿瘤细胞。在这里，我们研究了cADPR和热对[Ca 2 +] i的共激活机制是否发生在小鼠完整的下丘脑神经元中。在35 °C下，将cADPR细胞外应用于从雄性ICR小鼠下丘脑前部解剖的培养下丘脑细胞会升高[Ca 2 +] i，并且在高达39 °C的更高温度下[Ca 2 +] i升高显著增强。这种[Ca ~（2+）] i增加被ADPR和β-NAD ~+不同地模拟，但被cADPR拮抗剂8-Bromo-cADPR和ryanodine或2-aminoethoxydiphenyl borate（TRPM 2通道拮抗剂）阻断。cADPR和高温可使下丘脑视上核神经元[Ca 2 +] i升高，OT也可使神经元[Ca 2 +] i升高。TRPM 2阳离子通道的mRNA在ICR品系的小鼠下丘脑和人中表达。这些结果表明，cADPR依赖的Ca 2+动员和热敏TRPM 2依赖的阳离子内流都有助于下丘脑神经元[Ca 2 +] i升高，这可能有助于下丘脑OT分泌。
Oxytocin (OT) is synthesized and released in the hypothalamus, and plays a critical role in social recognition and behavior in mammals. Brain OT release is largely due to elevation of intracellular cytosolic calcium concentrations ([Ca2+] i ) induced by mobilization of Ca2+ from Ca2+ pools by cyclic ADP-ribose (cADPR) catalyzed by the ADP-ribosyl cyclase activity of CD38. Recently, we reported that extracellular application of cADPR, together with heat, increased [Ca2+] i in cultured neuronal tumor cells. Here, we examined whether this co-activation mechanism on [Ca2+] i by cADPR and heat occurs in intact hypothalamic neurons of mice. Extracellular application of cADPR to cultured hypothalamic cells dissected from the anterior hypothalamus of male ICR mice elevated [Ca2+] i at 35 °C, and the [Ca2+] i elevation was significantly enhanced at much higher temperatures up to 39 °C. This [Ca2+] i increase was mimicked differentially by ADPR and β-NAD+, but blocked by cADPR antagonists, 8-Bromo-cADPR and ryanodine, or 2-aminoethoxydiphenyl borate, a TRPM2 channel antagonist. The [Ca2+] i elevation was enhanced by cADPR and high temperature in neurons dissociated from the supraoptic nucleus of the hypothalamus, in which application of OT also increased [Ca2+] i . mRNA of TRPM2 cation channels were expressed in the mouse hypothalamus of the ICR strain and humans. These results suggest that both cADPR-dependent Ca2+ mobilization and heat-sensitive TRPM2-dependent cation influx contribute to the [Ca2+] i elevation in hypothalamic neurons, which may contribute to OT secretion in the hypothalamus.