Michalek H, Fortuna S, Pintor A
Laboratory of Pharmacology, Istituto Superiore di Sanita, Roma, Italy.
Acta Neurobiol Exp (Wars). 1993;53(1):93-101.
Age-related differences in the response of the cerebral cortex and ileum strip to a repeated treatment with an anticholinesterase compound, diisopropyl fluorophosphate (DFP) were evaluated in 3- and 24-month Sprague-Dawley rats. The response was measured in terms of acetylcholinesterase (AChE) inhibition and total muscarinic receptor density (MAChRs, measured as 3H-QNB binding). At the end of DFP treatment there was a 75% inhibition of brain AChE and 30% inhibition of ileal AChE, independently of age. The adaptive down-regulation of brain MAChRs was more pronounced in aged than in young rats (50 and 25%, respectively), while that of ileal MAChRs was greater in young than in aged rats (50 and 35%). The normalization of cortical MAChRs was delayed in aged rats that of ileal MAChRs was delayed in young rats. As regards age-related changes of AChE and MAChRs in untreated rats, there was a 30% decrease of cortical and ileal AChE, no changes in Bmax of cortical MAChRs and a 45% deficit of ileal MAChRs. This was accompanied by only a little age-related decrease in sensitivity of the isolated ileum to cholinergic agonists. Additional experiments on the responsiveness of phosphatidyl inositol system stimulated with carbachol showed that accumulation of inositol phosphate both in cortical and ileum strip slices was higher in aged than in young rats. The overall data indicate that treatment- and age-related changes of AChR mechanisms in the ileum strip differ considerably from those in the brain. However, the increased efficiency of post-receptor mechanisms in old age is their common feature.
在3个月和24个月大的斯普拉格-道利大鼠中，评估了大脑皮层和回肠条对重复给予抗胆碱酯酶化合物二异丙基氟磷酸酯（DFP）的反应中的年龄相关差异。反应通过乙酰胆碱酯酶（AChE）抑制和总毒蕈碱受体密度（MAChRs，以3H-QNB结合测量）来衡量。在DFP治疗结束时，无论年龄大小，脑AChE均有75%的抑制，回肠AChE有30%的抑制。老年大鼠脑MAChRs的适应性下调比年轻大鼠更明显（分别为50%和25%），而回肠MAChRs的适应性下调在年轻大鼠中比老年大鼠更大（50%和35%）。老年大鼠皮层MAChRs的正常化延迟，年轻大鼠回肠MAChRs的正常化延迟。关于未治疗大鼠中AChE和MAChRs的年龄相关变化，皮层和回肠AChE降低了30%，皮层MAChRs的Bmax无变化，回肠MAChRs减少了45%。这仅伴随着离体回肠对胆碱能激动剂的敏感性有轻微的年龄相关下降。用卡巴胆碱刺激磷脂酰肌醇系统的反应性的额外实验表明，老年大鼠皮层和回肠条切片中肌醇磷酸的积累均高于年轻大鼠。总体数据表明，回肠条中AChR机制的治疗相关和年龄相关变化与大脑中的变化有很大差异。然而，老年时受体后机制效率的提高是它们的共同特征。
