Gibson R E, Zeeberg B R, Melograna J M, Wang T F, Ruch J, Braun A, Reba R C
George Washington University Medical Center, Washington, D.C.
Brain Res. 1991 Jul 5;553(1):110-6. doi: 10.1016/0006-8993(91)90237-p.
The in vivo washout kinetics of [3H]quinuclidinyl benzilate ([3H]QNB) varies significantly in various structures in the rat brain. The slowest washout rates are from the hippocampus, corpus striatum, and cortex, intermediate rates are exhibited from the thalamus and colliculi, while the fastest washout rate is from the cerebellum. We have also demonstrated a difference in the in vitro dissociation rates (k-1) of [3H]QNB from various structures. The k-1 for the hippocampus, corpus striatum and cortex, is two-fold slower than that observed in the thalamus, colliculi, and cerebellum. The differences in the in vitro dissociation kinetics are not, however, sufficient to explain the differences in the in vivo washout kinetics. We have developed a theoretical formulation which describes conditions under which the washout kinetics are a function of the concentration of receptor in a structure. Furthermore, we present a graphical method in which a plot of the reciprocal of the observed washout rate constant, 1/k(obs), vs receptor concentration is linear. Analysis of the washout kinetics of [3H]QNB from various structures of the CNS of rat were well described by this theory when the differences in in vitro k-1 are included.
[3H]东莨菪碱([3H]QNB)在大鼠脑内不同结构中的体内洗脱动力学差异显著。洗脱速率最慢的是海马体、纹状体和皮质，丘脑和丘脑中的洗脱速率处于中等水平，而小脑的洗脱速率最快。我们还证明了[3H]QNB在不同结构中的体外解离速率(k-1)存在差异。海马体、纹状体和皮质的k-1比在丘脑、丘脑和小脑中观察到的慢两倍。然而，体外解离动力学的差异不足以解释体内洗脱动力学的差异。我们已经开发了一种理论公式，该公式描述了洗脱动力学是结构中受体浓度函数的条件。此外，我们提出了一种图形方法，其中观察到的洗脱速率常数的倒数1/k(obs)与受体浓度的关系图是线性的。当考虑体外k-1的差异时，该理论很好地描述了大鼠中枢神经系统不同结构中[3H]QNB的洗脱动力学分析。
