Fluharty S J, Rabow L E, Zigmond M J, Stricker E M
J Pharmacol Exp Ther. 1985 Nov;235(2):354-60.
Subtotal destruction of central noradrenergic neurons with the neurotoxin, 6-hydroxydopamine, is known to increase tyrosine hydroxylase (TH) activity within surviving nerve terminals. The present report demonstrates a similar, dose-related elevation of TH activity in the adrenal medulla and sympathetic nerves after systemic 6-hydroxydopamine treatment. Two temporally distinct processes were observed in the sympathetic nerves: a rapid activation of TH, present during the first few days after the lesion, and a more gradual increase in maximal TH activity, most probably due to enzyme induction. In this regard, the stimulatory effect on catecholamine biosynthesis of cyclic AMP-dependent phosphorylation was attenuated substantially within cardiac sympathetic nerves 3 days after the lesion, but by 3 weeks the efficacy of cyclic AMP-dependent phosphorylation was restored completely. Similarly, the normal activation of cardiac TH activity elicited by insulin-induced hypoglycemia and cold stress was absent soon after 6-hydroxydopamine treatment, but returned 3 weeks later. These latter findings suggest that the adaptations within the sympathoadrenal system after subtotal sympathectomy can preclude further adaptations to stress.
已知用神经毒素6-羟基多巴胺对中枢去甲肾上腺素能神经元进行部分破坏会增加存活神经末梢内的酪氨酸羟化酶（TH）活性。本报告表明，全身给予6-羟基多巴胺治疗后，肾上腺髓质和交感神经中TH活性有类似的剂量相关升高。在交感神经中观察到两个时间上不同的过程：损伤后的头几天内TH迅速激活，以及最大TH活性更逐渐增加，很可能是由于酶诱导。在这方面，损伤后3天内心脏交感神经中对环磷酸腺苷（cAMP）依赖性磷酸化对儿茶酚胺生物合成的刺激作用大幅减弱，但到3周时cAMP依赖性磷酸化的效力完全恢复。同样，6-羟基多巴胺治疗后不久，胰岛素诱导的低血糖和冷应激引起的心脏TH活性正常激活消失，但3周后恢复。后一项发现表明，部分交感神经切除术后交感肾上腺系统内的适应性变化可能会阻止对压力的进一步适应。
