Marks M J, Romm E, Campbell S M, Collins A C
Institute for Behavioral Genetics and School of Pharmacy, University of Colorado, Boulder 80309.
Pharmacol Biochem Behav. 1989 Jul;33(3):679-89. doi: 10.1016/0091-3057(89)90407-3.
The specific binding of L-nicotine and alpha-bungarotoxin, two ligands which label different populations of putative nicotinic receptors, was determined in eight brain regions of 19 inbred mouse strains. The dissociation constants for L-nicotine (average = 2.26 nM) and alpha-bungarotoxin (average = 0.31 nM) did not vary significantly among the brain regions or strains. In contrast, significant variability among the maximal binding sites was observed between regions and among the strains within a region. Significant differences in L-nicotine binding were observed among the strains in midbrain, hindbrain, hippocampus, hypothalamus and colliculi, while little variability was noted in cortex or cerebellum. In general, those strains that had high L-nicotine binding in one region had high nicotine binding in the other regions. The strains clustered into two large groups: one group expressing relatively low binding and a second group expressing relatively high binding. Significant differences in alpha-bungarotoxin binding were observed in seven of the eight regions measured and, in general, those strains with high binding in one region tended to have high binding in the other regions. The strains clustered into three groups: those with low binding (DBA/1 and DBA/2), those with high binding (ST/b alone) and those with intermediate binding (the remaining 16 strains). The amount of binding of the two ligands did not correlate with each other. Comparison of nicotinic ligand binding with physiological response to nicotine suggests a relationship of L-nicotine binding with several responses observed after injection of low doses of nicotine and a relationship between alpha-bungarotoxin binding and nicotine-induced seizures.
在19个近交系小鼠品系的八个脑区中，测定了L-尼古丁和α-银环蛇毒素这两种标记不同假定烟碱样受体群体的配体的特异性结合。L-尼古丁（平均 = 2.26 nM）和α-银环蛇毒素（平均 = 0.31 nM）的解离常数在不同脑区或品系之间没有显著差异。相比之下，在不同脑区之间以及同一脑区内的不同品系之间，观察到最大结合位点存在显著差异。在中脑、后脑、海马体、下丘脑和丘脑中，不同品系之间的L-尼古丁结合存在显著差异，而在皮质或小脑中观察到的变异性较小。一般来说，那些在一个区域具有高L-尼古丁结合的品系在其他区域也具有高尼古丁结合。这些品系聚为两大类：一类表达相对较低的结合，另一类表达相对较高的结合。在测量的八个区域中的七个区域观察到α-银环蛇毒素结合存在显著差异，并且一般来说，那些在一个区域具有高结合的品系在其他区域往往也具有高结合。这些品系聚为三组：低结合组（DBA/1和DBA/2）、高结合组（仅ST/b）和中等结合组（其余16个品系）。两种配体的结合量彼此不相关。将烟碱样配体结合与对尼古丁的生理反应进行比较表明，L-尼古丁结合与注射低剂量尼古丁后观察到的几种反应之间存在关系，以及α-银环蛇毒素结合与尼古丁诱发的癫痫发作之间存在关系。
