Waters S M, David T P
Department of Pharmacology, University of Arizona College of Medicine, Tucson, USA.
J Gerontol A Biol Sci Med Sci. 1995 Sep;50(5):B315-9. doi: 10.1093/gerona/50a.5.b315.
The levels of specific neuropeptides and the activity of neuropeptidases known to degrade neuropeptides have been shown to be altered in senile dementia of the Alzheimer's type (SDAT) postmortem brain. We examined the metabolism of exogenous substance P, a neuropeptide with a putative role in SDAT pathology, in human postmortem temporal cortex, hippocampus, and caudate membrane homogenates from SDAT and sex- and age-matched control brain. The activity of two neuropeptidases known to metabolize substance P, neutral endopeptidase E.C.3.4.24.11 and metalloendopeptidase E.C.3.4.24.15, was also determined in the same postmortem, human tissue samples. The metabolic half-life of substance P was significantly increased in SDAT, postmortem, temporal cortex. The increased half-life of substance P was correlated with a decreased activity of the metabolic enzyme metalloendopeptidase 24.15 in temporal cortex. Substance P metabolism was not significantly altered in hippocampus or caudate tissues from SDAT brain compared to controls. The alteration of neuropeptidases demonstrated in this study and as shown by altered substance P metabolism may have a significant effect on the level of several biologically important neuropeptides in SDAT brain.
在阿尔茨海默病型老年痴呆症（SDAT）的尸检大脑中，特定神经肽的水平以及已知可降解神经肽的神经肽酶的活性已被证明发生了改变。我们检测了外源性P物质（一种在SDAT病理学中可能起作用的神经肽）在来自SDAT以及性别和年龄匹配的对照大脑的人类尸检颞叶皮质、海马体和尾状核膜匀浆中的代谢情况。在相同的尸检人类组织样本中，还测定了两种已知可代谢P物质的神经肽酶的活性，即中性内肽酶E.C.3.4.24.11和金属内肽酶E.C.3.4.24.15。在SDAT尸检颞叶皮质中，P物质的代谢半衰期显著延长。P物质半衰期的延长与颞叶皮质中代谢酶金属内肽酶24.15的活性降低相关。与对照组相比，SDAT大脑海马体或尾状核组织中的P物质代谢没有显著改变。本研究中所证实的神经肽酶的改变以及P物质代谢的改变，可能会对SDAT大脑中几种具有生物学重要性的神经肽水平产生显著影响。
