Tsai H, Hewitt C W, Buchholz J N, Duckles S P
Department of Pharmacology, College of Medicine, University of California, Irvine 92697, USA.
Neurobiol Aging. 1997 Mar-Apr;18(2):229-33. doi: 10.1016/s0197-4580(97)00005-5.
Stimulation-evoked norepinephrine release from rat tail artery adrenergic nerves increased with advancing age in the Fischer-344 rat when function of norepinephrine uptake mechanisms and prejunctional alpha-2 adrenoceptors were blocked. When calcium channels were bypassed with the ionophore, ionomycin (4 microM), norepinephrine release from aged nerves (20 months) was still elevated as compared to 6-month-old nerves. Norepinephrine release stimulated by high K+ was also higher in 20-month nerves. The intracellular calcium chelator, 1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetomethylester (BAPTA/AM), was used to determine whether age-related increases in norepinephrine release could be reversed with the addition of an artificial intracellular calcium buffer. Exposure to BAPTA/AM decreased stimulation-evoked norepinephrine release in both old and young tail arteries; however, the effect was significantly greater in older arteries. When mitochondrial calcium uptake was compromised using the uncoupler of mitochondrial oxidative phosphorylation, dinitrophenol, BAPTA caused a further decrease in stimulation-evoked norepinephrine release in 20-month tail arteries with much less effect in 6-month-old nerves. These results suggest that intracellular calcium buffering is less efficient in older nerves.
当去甲肾上腺素摄取机制和接头前α₂肾上腺素能受体的功能被阻断时，在Fischer-344大鼠中，刺激诱发的大鼠尾动脉肾上腺素能神经释放的去甲肾上腺素随着年龄的增长而增加。当用离子载体离子霉素（4 microM）绕过钙通道时，与6月龄神经相比，老龄神经（20个月）释放的去甲肾上腺素仍然升高。在20月龄神经中，高钾刺激引起的去甲肾上腺素释放也更高。细胞内钙螯合剂1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸甲酯（BAPTA/AM）被用于确定是否可以通过添加人工细胞内钙缓冲剂来逆转与年龄相关的去甲肾上腺素释放增加。暴露于BAPTA/AM可降低老龄和幼龄尾动脉中刺激诱发的去甲肾上腺素释放；然而，在老龄动脉中的作用明显更大。当使用线粒体氧化磷酸化解偶联剂二硝基苯酚损害线粒体钙摄取时，BAPTA导致20月龄尾动脉中刺激诱发的去甲肾上腺素释放进一步减少，而对6月龄神经的作用小得多。这些结果表明，老龄神经中的细胞内钙缓冲效率较低。
