Snyder D L, Aloyo V J, Wang W, Roberts J
Department of Pharmacology, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129, USA.
J Cardiovasc Pharmacol. 1998 Dec;32(6):896-901. doi: 10.1097/00005344-199812000-00005.
The purpose of this study was to determine whether aging alters neuronal uptake of norepinephrine (NE) in the rat heart and if dietary restriction influenced the effect of age on this system. Cardiac synaptosomes were prepared from 6-, 12- and 24-month-old male F344 rats fed ad libitum (AL) or a diet restricted (DR) to 60% of AL intake. Cardiac synaptosomes were incubated with 50, 100, 200, or 400 nM [3H]NE for 10 min at 37 degrees C with and without desmethylimipramine (DMI), a selective neuronal-uptake blocker. DMI-sensitive [3H]NE uptake was calculated as the difference between samples with and without DMI. NE uptake was adjusted for the number of cardiac synaptosomes in each sample by dividing by the endogenous NE content in each sample. The Vmax for uptake ([3H]NE/min/ng NE) declined significantly between 6 and 12 months in AL rats and between 12 and 24 months in DR rats. Km was not significantly different between age or diet groups. The change in Vmax with age suggests that the number of NE transporters per synaptosome may decline with age and that DR delays this effect of age. There were no differences in the sensitivity to DMI between age or diet groups.
本研究的目的是确定衰老是否会改变大鼠心脏中去甲肾上腺素(NE)的神经元摄取,以及饮食限制是否会影响年龄对该系统的作用。从自由摄食(AL)或饮食限制(DR,摄入量为AL的60%)的6个月、12个月和24个月大的雄性F344大鼠制备心脏突触体。在有和没有选择性神经元摄取阻滞剂去甲丙咪嗪(DMI)的情况下,将心脏突触体与50、100、200或400 nM [3H]NE在37℃下孵育10分钟。DMI敏感的[3H]NE摄取量计算为有和没有DMI的样品之间的差异。通过除以每个样品中的内源性NE含量,对每个样品中心脏突触体的数量进行NE摄取量调整。在AL大鼠中,摄取的Vmax([3H]NE/分钟/纳克NE)在6至12个月之间显著下降,在DR大鼠中,在12至24个月之间显著下降。年龄组或饮食组之间的Km没有显著差异。Vmax随年龄的变化表明,每个突触体中NE转运体的数量可能会随着年龄的增长而下降,并且DR会延迟年龄对这种作用的影响。年龄组或饮食组之间对DMI的敏感性没有差异。