Neuronal sodium homoeostatis and axoplasmic amine concentration determine calcium-independent noradrenaline release in normoxic and ischemic rat heart.
Neuronal sodium homoeostatis and axoplasmic amine concentration determine calcium-independent noradrenaline release in normoxic and ischemic rat heart.
复制标题
神经元钠稳态和轴浆胺浓度决定常氧和缺血大鼠心脏中钙独立的去甲肾上腺素释放。
作者：
A. Schomig;T. Kurz;G. Richardt;Edgar Schomig
研究了正常氧合、氰化物中毒和缺血条件下大鼠离体灌注心脏钙非依赖性去甲肾上腺素的释放。采用高效液相色谱法测定内源性去甲肾上腺素和二羟基苯乙二醇的释放量。神经细胞的主要去甲肾上腺素代谢物二羟基苯乙二醇的释放作为游离轴浆胺浓度的指标。当Ro 4-1284或三甲基锡干扰神经元囊泡的储存功能时，观察到二羟基苯乙二醇的高释放，但未伴有去甲肾上腺素的溢出。然而，如果这些药物与抑制Na+K+- atp酶或与缬草碱诱导的钠进入神经元联合使用，二羟基苯乙二醇和去甲肾上腺素都被释放。去甲肾上腺素的释放不依赖于细胞外钙，并被阻断神经元儿茶酚胺摄取（摄取1）所抑制，表明非胞外性去甲肾上腺素从交感神经末梢释放。这种释放主要取决于两个条件：1)交感神经元内去甲肾上腺素细胞质浓度的增加和2)神经元内钠的积累。这两种条件一起是诱导去甲肾上腺素通过质膜外排的必要条件，利用摄取载体以与正常运输方向相反的方式进行外排。由氰化物中毒或缺血引起的交感神经元能量状态紊乱，同样通过干扰囊泡储存功能和神经元钠稳态，引起钙非依赖性去甲肾上腺素释放。同样，释放对摄取阻断很敏感。由于神经元钠积累是限速步骤，当残留的Na+，K+- atp酶活性受到抑制时，释放进一步加快。Na+-H+交换是钠在缺血时进入交感神经末段的主要途径，阿米洛利和乙基异丙胺洛利对Na+-H+交换的抑制作用可显著抑制缺血诱导的去甲肾上腺素释放。
Calcium-independent noradrenaline release was studied in the isolated perfused rat heart under conditions of normoxia, cyanide intoxication, and ischemia. The release of endogenous noradrenaline and dihydroxyphenylglycol were determined by high-performance liquid chromatography. The release of dihydroxyphenylglycol, the main neuronal noradrenaline metabolite, was used as an indicator of the free axoplasmic amine concentration. When storage function of neuronal vesicles was disturbed by Ro 4-1284 or trimethyltin, high dihydroxyphenylglycol release was observed without concomitant overflow of noradrenaline. If, however, these agents were combined with inhibition of Na+K+-ATPase or with veratridine-induced entry of sodium into the neuron, both dihydroxyphenylglycol and noradrenaline were released. Noradrenaline release was independent of extracellular calcium and was suppressed by blockade of neuronal catecholamine uptake (uptake1), indicating nonexocytotic noradrenaline liberation from the sympathetic nerve ending. This release critically depended on two conditions: 1) increased cytoplasmic concentrations of noradrenaline within the sympathetic neuron and 2) intraneuronal sodium accumulation. Both conditions together were required to induce noradrenaline efflux across the plasma membrane using the uptake1 carrier in reverse of its normal transport direction. A disturbed energy status of the sympathetic neuron, induced by cyanide intoxication or ischemia, likewise caused calcium-independent noradrenaline release by interfering with both vesicular storage function and neuronal sodium homoeostatis. Again, release was sensitive to uptake1 blockade. Since neuronal sodium accumulation was the rate-limiting step, release was further accelerated when residual Na+,K+-ATPase activity was inhibited. Na+-H+ exchange was identified as the predominant pathway of sodium entry into the sympathetic nerve ending in ischemia, and its inhibition by amiloride and ethylisopropylamiloride markedly suppressed ischemia-induced noradrenaline release.
登录
查看更多内容
灌注大鼠心脏的 23Na 和 39K 核磁共振研究。
影响因子：
3.4
作者：
Pike,MM;Frazer,JC;Dedrick,DF;Ingwall,JS;Allen,PD;SpringerJr,CS;Smith,TW
通讯作者：
Smith,TW
儿茶酚胺在狗心脏缺血区的重新分布。
DOI：
--
发表时间：
1984
期刊：
The American journal of pathology
影响因子：
--
作者：
Muntz,KH;Hagler,HK;Boulas,HJ;Willerson,JT;Buja,LM
通讯作者：
Buja,LM
DOI：
10.1016/s0021-9258(18)33879-1
发表时间：
1982-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Johnson;M. Beers;A. Scarpa
通讯作者：
R. Johnson;M. Beers;A. Scarpa
正常和胺菊酯修饰的单钠通道的电压依赖性钙阻断。
影响因子：
3.4
作者：
Yamamoto,D;Yeh,JZ;Narahashi,T
通讯作者：
Narahashi,T