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去甲肾上腺素的合成与利用:在正常条件下以及用α-肾上腺素能受体阻断剂治疗后受神经冲动流的控制。

Noradrenaline synthesis and utilization: control by nerve impulse flow under normal conditions and after treatment with alpha-adrenoreceptor blocking agents.

作者信息

Grabowska M, Andén N E

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1976;292(1):53-8. doi: 10.1007/BF00506489.

Abstract

The changes in the synthesis and utilization or noradrenaline cranial and caudal to an acute section of the rat spinal cord have been used to investigate the importance of nerve impulses for these processes. 1. Cranial to a lesion of the spinal cord, the alpha-methyltyrosine-induced disappearance of noradrenaline was accelerated by the alpha-adrenoreceptor blocking agents yohimbine (10 mg/kg), piperoxan (60 mg/kg) and tolazoline (50 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, this disappearance was decelerated as compared to that cranial to the lesion and it was not influenced by the three alpha-adrenoreceptor blocking agents. 2. The nialamide-induced accumulation of normetanephrine in the whole brain was increased by phenoxybenzamine (20 mg/kg) and yohimbine whereas it was decreased by the alpha-adrenoreceptor stimulating agent clonidine (0.1 mg/kg). The effect of clonidine was completely antagonized by yohimbine, but not by phenoxybenzamine, giving further evidence for the view that clonidine and yohimbine have a stronger effect than phenoxybenzamine on the alpha-adrenoreceptors regulating the release of noradrenaline induced by nerve impluses. 3. The accumulation of Dopa after decarboxylase inhibition cranial to a lesion of the spinal cord was accelerated by yohimbine, piperoxan and tolazoline, but not significantly affected by phenoxybenzamine and haloperidol (10 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, the popa accumulation was decelerated as compared to that cranial to the lesion and it was not influenced by the former three alpha--adrenoreceptor blocking agents as well as by clonidine. 4. The results show that the synthesis and the utilization noradrenaline normally, as well as the accelerations of these processes by alpha-adrenoreceptor blocking agents, are dependent on nerve impulses. The stimulation of the synthesis and utilization of noradrenaline by nerve impulses might by influenced via the activity of teh alpha-adrenoreceptors located either on the nerve terminals or on the cell bodies or on both parts of the noradrenergic neurones. In the absence of nerve impulses, a receptor-mediated feedback mechanism similar to that described for the synthesis of dopamine does not appear to regulate the synthesis of noradrenaline.

摘要

通过研究大鼠脊髓急性横断后去甲肾上腺素在头端和尾端的合成、利用变化,来探讨神经冲动对这些过程的重要性。1. 在脊髓损伤头端,α-甲基酪氨酸诱导的去甲肾上腺素消失,可被α-肾上腺素能受体阻断剂育亨宾(10毫克/千克)、哌罗克生(60毫克/千克)和妥拉唑啉(50毫克/千克)加速。在脊髓损伤尾端缺乏神经冲动时,与损伤头端相比,这种消失减慢,且不受这三种α-肾上腺素能受体阻断剂影响。2. 苯氧苄胺(20毫克/千克)和育亨宾可增加尼亚酰胺诱导的全脑中去甲变肾上腺素的蓄积,而α-肾上腺素能受体激动剂可乐定(0.1毫克/千克)则使其减少。可乐定的作用被育亨宾完全拮抗,但不被苯氧苄胺拮抗,这进一步证明了可乐定和育亨宾对调节神经冲动诱导的去甲肾上腺素释放的α-肾上腺素能受体的作用比苯氧苄胺更强的观点。3. 在脊髓损伤头端抑制脱羧酶后多巴的蓄积,可被育亨宾、哌罗克生和妥拉唑啉加速,但不受苯氧苄胺和氟哌啶醇(10毫克/千克)显著影响。在脊髓损伤尾端缺乏神经冲动时,与损伤头端相比,多巴蓄积减慢,且不受前三种α-肾上腺素能受体阻断剂以及可乐定影响。4. 结果表明,去甲肾上腺素的正常合成和利用,以及α-肾上腺素能受体阻断剂对这些过程的加速作用,均依赖于神经冲动。神经冲动对去甲肾上腺素合成和利用的刺激可能通过位于去甲肾上腺素能神经元神经末梢或细胞体或两者上的α-肾上腺素能受体的活性来影响。在缺乏神经冲动时,一种类似于多巴胺合成中所描述的受体介导的反馈机制似乎并不调节去甲肾上腺素的合成。

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