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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Endothelin-1 and -3 modulate the neuronal norepinephrine transporter through multiple signalling pathways in the rat posterior hypothalamus.
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Endothelin-1 and -3 modulate the neuronal norepinephrine transporter through multiple signalling pathways in the rat posterior hypothalamus.

机译:内皮素-1和-3通过大鼠下丘脑后部的多种信号通路调节神经元去甲肾上腺素转运蛋白。

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We have previously reported that endothelin-1 and -3 modulate different steps of noradrenergic transmission in the hypothalamus. We showed that endothelins modify neuronal norepinephrine transport activity through the regulation of the kinetic constant and internalization. In the present work we sought to define the endothelin receptors and intracellular mechanisms involved in the down-regulation of neuronal norepinephrine uptake induced by endothelin-1 and -3 in the rat posterior hypothalamic region. Results showed that endothelin-1 reduced norepinephrine uptake through ET(B) receptors, whereas endothelin-3 through a non-conventional or atypical endothelin receptor. In both cases, the effect on norepinephrine uptake was coupled to protein kinase A and C as well as nitric oxide pathways. However, neither protein kinase G nor intracellular or extracellular calcium and calcium/calmodulin-dependent protein kinase II were involved. In addition, the same intracellular mechanisms participated in the reduction of nisoxetine binding (norepinephrine transporter internalization index) induced by both endothelins. Present findings reveal the underlying mechanisms involved in the regulation of the neuronal norepinephrine transporter by endothelins and further support the role of these peptides in the modulation of noradrenergic transmission at the presynaptic nerve endings in the posterior hypothalamus.
机译:我们以前曾报道过内皮素-1和-3调节下丘脑中去甲肾上腺素能传递的不同步骤。我们表明内皮素通过调节动力学常数和内在化作用来修饰神经元去甲肾上腺素的转运活性。在目前的工作中,我们试图确定内皮素受体和细胞内机制参与大鼠下丘脑后区由内皮素-1和-3诱导的神经元去甲肾上腺素摄取的下调。结果显示内皮素-1减少了通过ET(B)受体的去甲肾上腺素的摄取,而内皮素-3则通过非常规或非典型内皮素受体的摄取。在这两种情况下,对去甲肾上腺素摄取的影响都与蛋白激酶A和C以及一氧化氮途径有关。然而,既不涉及蛋白激酶G,也不涉及细胞内或细胞外钙和钙/钙调蛋白依赖性蛋白激酶II。另外,相同的细胞内机制参与了两种内皮素诱导的尼索西汀结合的降低(去甲肾上腺素转运蛋白内化指数)。目前的发现揭示了内皮素调节神经元去甲肾上腺素转运蛋白的潜在机制,并进一步支持这些肽在下丘脑后突触前神经末梢的去甲肾上腺素能传递的调节中的作用。

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