Zubieta J K, Frey K A
Mental Health Research Institute, University of Michigan, Ann Arbor.
J Pharmacol Exp Ther. 1993 Jan;264(1):415-22.
The regional distribution of putative M3 receptors was studied by quantitative autoradiography of rat brain sections labeled with 4-diphenylacetoxy-N-methyl-piperidine methioxide. The radioligand appears to label multiple muscarinic receptor subtypes in direct binding assays, as evidenced by competition experiments with unlabeled pirenzepine and 11-([2-[(2-(diethylamino)methyl]-1- piperidinyl]acetyl-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodi azepine-6-on. Conditions favoring the selective labeling of M3 receptors were determined on the basis of the competition studies and were subsequently applied to regional mapping of M3 receptor binding. Under the conditions used, autoradiographic images may be obtained with both 9-fold M3-to-M1 selectivity and 12-fold M3-to-M2 selectivity. Although distributed widely at relatively low prevalence throughout the neuraxis, M3 receptors are apparently enriched relative to M1 and M2 receptors in several diencephalic and brain stem regions including thalamic and hypothalamic nuclei, the substantia nigra, superior colliculus, periaqueductal gray and the pons. The present results suggest that the binding of 4-diphenylacetoxy-N-methyl-piperidine methioxide, under appropriate conditions, may permit direct estimation of M3 receptors in mammalian brain.
通过用4-二苯基乙酰氧基-N-甲基哌啶甲磺酸标记大鼠脑切片的定量放射自显影术研究了假定的M3受体的区域分布。在直接结合试验中，放射性配体似乎标记了多种毒蕈碱受体亚型，与未标记的哌仑西平和11-([2-[(2-(二乙氨基)甲基]-1-哌啶基]乙酰基-5,11-二氢-6H-吡啶并[2,3-b][1,4]苯并二氮杂卓-6-酮的竞争实验证明了这一点。基于竞争研究确定了有利于M3受体选择性标记的条件，随后将其应用于M3受体结合的区域定位。在所使用的条件下，可以获得具有9倍M3对M1选择性和12倍M3对M2选择性的放射自显影图像。尽管M3受体在整个神经轴中以相对较低的发生率广泛分布，但在包括丘脑和下丘脑核、黑质、上丘、导水管周围灰质和脑桥在内的几个间脑和脑干区域中，相对于M1和M2受体，M3受体明显富集。目前的结果表明，在适当条件下，4-二苯基乙酰氧基-N-甲基哌啶甲磺酸的结合可能允许直接估计哺乳动物脑中的M3受体。
