Khalil Z, Sanderson K, Isberg P, Bassirat M, Livett B, Helme R
National Research Institute of Gerontology and Geriatric Medicine, North West Hospital (Mount Royal Campus), Parkville, Melbourne, Vic., Australia.
Brain Res. 1994 Jul 18;651(1-2):227-35. doi: 10.1016/0006-8993(94)90701-3.
The primary constituent of the senile plaque core in Alzheimer's disease (AD) is the beta-amyloid protein (beta A4). A discrete 11 amino acid fragment of the beta A4, beta A4(25-35), has been implicated in mediating in vitro neurotoxicity and an inflammatory response surrounding senile plaques in AD via interaction with the Serpin Enzyme Complex (SEC) receptor. Substance P (SP), a neuropeptide of the tachykinin family and a major mediator of neurogenic inflammation, shows sequence homology to beta A4(25-35) and has been shown to protect against the neurotoxicity of beta-amyloid. SP also competes with beta A4(25-35) for binding to the SEC-receptor. SP neurons have also been found to be depleted in AD. Using a blister model of inflammation in the rat hind footpad, we have examined the effect of beta A4(25-35) and its interaction with SP in rat skin microvasculature and determined age-related changes to these phenomena. In addition, pharmacological manipulation of these responses using SEC-receptor ligands (peptide 105Y and 105C) was also undertaken. Because of the evidence for co-existence and co-release of SP and calcitonin gene-related peptide (CGRP) from the peripheral terminals of sensory nerves, it was of interest to examine the interaction of CGRP with beta A4(25-35) on rat skin microvasculature. beta A4(25-35) (10 microM) was perfused over the base of a blister raised on the hind footpad of anaesthetised young and old rats. This was followed by perfusion of SP (1 microM) or CGRP (1 microM) after Ringer's solution. Relative blood flow was monitored using a Laser-Doppler Flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS)
阿尔茨海默病（AD）中老年斑核心的主要成分是β-淀粉样蛋白（βA4）。βA4的一个由11个氨基酸组成的离散片段βA4(25 - 35)，被认为通过与丝氨酸蛋白酶抑制剂酶复合物（SEC）受体相互作用，在体外介导神经毒性以及AD中老年斑周围的炎症反应。P物质（SP）是速激肽家族的一种神经肽，也是神经源性炎症的主要介质，与βA4(25 - 35)具有序列同源性，并且已被证明可抵御β-淀粉样蛋白的神经毒性。SP还与βA4(25 - 35)竞争结合SEC受体。在AD中也发现SP神经元有所减少。我们利用大鼠后足垫的炎症水疱模型，研究了βA4(25 - 35)的作用及其与SP在大鼠皮肤微血管中的相互作用，并确定了这些现象与年龄相关的变化。此外，还使用SEC受体配体（肽105Y和105C）对这些反应进行了药理学调控。由于有证据表明SP和降钙素基因相关肽（CGRP）在感觉神经外周终末共存并共同释放，因此研究CGRP与βA4(25 - 35)在大鼠皮肤微血管上的相互作用很有意义。将βA4(25 - 35)（10微摩尔）灌注到麻醉的年轻和老年大鼠后足垫上的水疱底部。随后在林格氏液灌注后灌注SP（1微摩尔）或CGRP（1微摩尔）。使用激光多普勒血流仪监测相对血流量。（摘要截短于250字）
