Chouinard M L, Gallagher M, Yasuda R P, Wolfe B B, McKinney M
Department of Pharmacology, Mayo Clinic, Jacksonville, FL 32224, USA.
Neurobiol Aging. 1995 Nov-Dec;16(6):955-63. doi: 10.1016/0197-4580(95)02015-2.
Efficiency of coupling of hippocampal muscarinic receptors to phosphoinositide (PI) turnover was investigated in behaviorally characterized young and aged Long-Evans rats using hippocampal minces and the method of partial receptor alkylation of Furchgott. Densities of the m1, m2, and m3 receptor proteins were determined using specific antibodies and immunoprecipitation. Spatial learning ability was quantified using a water maze. There were no differences in the levels of muscarinic receptor proteins between young and aged (27 months) rats or in rats with impaired spatial learning. The dissociation constant (KD) for the agonist oxotremorine-M and the KD/EC50 ratio, an indicator of receptor-effector coupling efficiency were similar in young and aged rats. However, the maximal PI turnover response to oxotremorine-M was decreased in impaired aged rats and this parameter was highly correlated with the spatial learning index (R = -0.825; p < 0.001). A reduction in effector stimulation in the absence of changes in receptor protein or coupling efficiency suggests that dysfunction in the hippocampal muscarinic receptor systems occurs at the level of phospholipase C or beyond.
利用海马切片和Furchgott的部分受体烷基化方法，在行为特征明确的年轻和老年Long-Evans大鼠中研究了海马毒蕈碱受体与磷酸肌醇（PI）周转的偶联效率。使用特异性抗体和免疫沉淀法测定m1、m2和m3受体蛋白的密度。使用水迷宫对空间学习能力进行量化。年轻和老年（27个月）大鼠之间或空间学习受损的大鼠之间，毒蕈碱受体蛋白水平没有差异。激动剂氧化震颤素-M的解离常数（KD）以及作为受体-效应器偶联效率指标的KD/EC50比值，在年轻和老年大鼠中相似。然而，在空间学习受损的老年大鼠中，对氧化震颤素-M的最大PI周转反应降低，并且该参数与空间学习指数高度相关（R = -0.825；p < 0.001）。在受体蛋白或偶联效率没有变化的情况下效应器刺激减少，表明海马毒蕈碱受体系统的功能障碍发生在磷脂酶C或更下游的水平。
