De Sarno P, Giacobini E, Downen M
Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62708.
J Neurosci Res. 1987;18(4):578-90. doi: 10.1002/jnr.490180411.
Acetylcholinesterase (AChE) can be released in the perfusate of rat caudate nucleus (CN) slices by two different modes of stimulation, with electrical stimulation at 5 Hz and with high concentrations of K+ (105 mM) using K+-propionate. We were unable to demonstrate AChE release with lower K+ concentrations (50 mM); however, at this concentration the drop in AChE activity seen in resting conditions was prevented. Practically all (95%) cholinesterase (ChE) found in the rat CN is AChE, which is represented by two major molecular forms (4S and 10S). In the perfusate, only AChE activity could be detected. A comparison of acetylcholine (ACh) and AChE release showed that maximal 3H-outflow and AChE release occurred at the same frequency (5 Hz), but the onset of AChE release was delayed. With high K+ (105 mM) depolarization, AChE release started after termination of the stimulation and continued for at least 50 min. These findings are consistent with the view that soluble form(s) of AChE can be slowly released from neurons under specific conditions of depolarization. In the caudate of the rat, the most likely sites for this release are processes of cholinergic interneurons. A hypothesis of AChE release is presented, and possible physiological and pathological implications of such a mechanism are discussed.
乙酰胆碱酯酶(AChE)可通过两种不同的刺激方式在大鼠尾状核(CN)切片的灌流液中释放,即5赫兹的电刺激以及使用丙酸钾的高浓度钾离子(105毫摩尔)刺激。我们无法证明在较低钾离子浓度(50毫摩尔)下AChE的释放;然而,在此浓度下,静息状态下观察到的AChE活性下降得到了阻止。实际上,在大鼠CN中发现的几乎所有(95%)胆碱酯酶(ChE)都是AChE,它以两种主要分子形式(4S和10S)存在。在灌流液中,只能检测到AChE活性。乙酰胆碱(ACh)和AChE释放的比较表明,最大3H流出量和AChE释放发生在相同频率(5赫兹),但AChE释放的起始延迟。在高钾(105毫摩尔)去极化时,AChE释放在刺激终止后开始,并持续至少50分钟。这些发现与以下观点一致,即AChE的可溶性形式在特定的去极化条件下可从神经元中缓慢释放。在大鼠尾状核中,这种释放最可能的部位是胆碱能中间神经元的突起。本文提出了AChE释放的假说,并讨论了这种机制可能的生理和病理意义。