Kurian P, Narang N, Crews F T
Department of Pharmacology, University of Florida College of Medicine, Gainesville 32610-0267.
Neurobiol Aging. 1992 Jul-Aug;13(4):521-6. doi: 10.1016/0197-4580(92)90081-8.
It is well established that muscarinic cholinergic receptors are linked to phosphoinositide hydrolysis in brain. Previous studies of muscarinic responses used Li+ to increase inositol phosphate accumulation and suggested little or no change during aging. Li+ disrupts certain aspects of the inositol phosphate metabolism and inhibits the formation of inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. Ins(1,3,4,5)P4 appears to have second messenger functions. To investigate the effects of aging on agonist stimulated Ins(1,3,4,5)P4 formation, young (6-8 months) and old (28-30 months) Fischer 344 rat cerebral cortical or hippocampal slices were challenged with various agonists known to stimulate phosphoinositide hydrolysis in brain using a recently developed assay that does not use Li+. Carbachol and quisqualate stimulated [3H]inositol trisphosphate ([3H]InsP3) and [3H]Ins(1,3,4,5)P4 formation in young and old rat cerebral cortical slices. Norepinephrine, 5-hydroxytryptamine, and vasopressin failed to stimulate [3H]Ins(1,3,4,5)P4 or [3H]InsP3 formation in either young or old rat cerebral cortical slices. In old rat cerebral cortical slices, the carbachol-stimulated [3H]Ins(1,3,4,5)P4 formation was reduced by 44%. Angiotensin II stimulated [3H]InsP3 was increased (219%) in old rats. There was no influence of aging either on the basal level or on the maximal response to carbachol or quisqualate in hippocampal slices. These studies suggest region-specific changes in phosphoinositide hydrolysis during aging.
毒蕈碱型胆碱能受体与大脑中的磷酸肌醇水解相关，这一点已得到充分证实。先前关于毒蕈碱反应的研究使用锂离子来增加肌醇磷酸的积累，并表明在衰老过程中变化很小或没有变化。锂离子会破坏肌醇磷酸代谢的某些方面，并抑制肌醇1,3,4,5-四磷酸[Ins(1,3,4,5)P4]的形成。Ins(1,3,4,5)P4似乎具有第二信使功能。为了研究衰老对激动剂刺激的Ins(1,3,4,5)P4形成的影响，使用一种最近开发的不使用锂离子的检测方法，用已知能刺激大脑中磷酸肌醇水解的各种激动剂对年轻（6-8个月）和年老（28-30个月）的Fischer 344大鼠大脑皮层或海马切片进行刺激。卡巴胆碱和喹啉酸刺激了年轻和年老大鼠大脑皮层切片中[3H]肌醇三磷酸([3H]InsP3)和[3H]Ins(1,3,4,5)P4的形成。去甲肾上腺素、5-羟色胺和血管加压素未能刺激年轻或年老大鼠大脑皮层切片中[3H]Ins(1,3,4,5)P4或[3H]InsP3的形成。在年老大鼠大脑皮层切片中，卡巴胆碱刺激的[3H]Ins(1,3,4,5)P4形成减少了44%。血管紧张素II刺激的[3H]InsP3在年老大鼠中增加（219%）。衰老对海马切片中的基础水平或对卡巴胆碱或喹啉酸的最大反应均无影响。这些研究表明衰老过程中磷酸肌醇水解存在区域特异性变化。
