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大鼠纹状体[3H]螺哌隆结合的个体发生发育:钠和鸟嘌呤核苷酸的调节作用

Ontogenetic development of the striatal [3H]spiperone binding: regulation by sodium and guanine nucleotide in rats.

作者信息

Nomura Y, Oki K, Segawa T

出版信息

J Neurochem. 1982 Apr;38(4):902-8. doi: 10.1111/j.1471-4159.1982.tb05328.x.

Abstract

Ontogenetic development of specific [3H]spiperone binding to crude synaptic membranes and its regulation by Na+ and GTP was investigated in the rat striatum. (d)-Butaclamol more effectively inhibited [3H]spiperone binding than (l)-butaclamol. The ratio of inhibitory activity of (d)- and (l)-butaclamol for [3H]spiperone binding was not different between 1-, 7-, and 70-day-old animals but eight- to ninefold lower at 18 days of gestation than during the postnatal period. A Scatchard plot of specific binding indicated the presence of two types of binding: low-affinity (KD = 1.51 nM) and high-affinity (KD = 0.09 nM) binding on day 70. Only one component (KD = 0.075 nM) was observed on days 1 and 7 and both types of binding were found on day 15. Bmax gradually increased with age and reached a peak on day 30, followed by a decline on days 70 and 360. Na+, 100 mM, significantly increased specific binding on days 1, 7, 15, and 70. GTP, 50 microM, completely reversed the Na+-induced decrease in IC50 of apomorphine on both days 15 and 70, but not on day 7. It is suggested that receptors could recognize ligand stereospecificity on day 1. The density in dopamine receptors in the striatum reaches a peak on day 30, followed by a decrease on days 70 and 360. In addition, regulation by Na+ and GTP in agonist binding to dopamine receptors seems to become functional between 1 and 2 weeks after birth.

摘要

在大鼠纹状体中研究了与粗制突触膜特异性结合的[³H]司哌罗宁的个体发生发育及其受Na⁺和GTP的调节。(d)-布他拉莫比(l)-布他拉莫更有效地抑制[³H]司哌罗宁的结合。(d)-和(l)-布他拉莫对[³H]司哌罗宁结合的抑制活性之比在1日龄、7日龄和70日龄动物之间没有差异,但在妊娠18天时比出生后时期低8至9倍。特异性结合的Scatchard图表明存在两种结合类型:70日龄时为低亲和力(KD = 1.51 nM)和高亲和力(KD = 0.09 nM)结合。在第1天和第7天仅观察到一个成分(KD = 0.075 nM),在第15天发现了两种结合类型。Bmax随年龄逐渐增加,在第30天达到峰值,随后在第70天和第360天下降。100 mM的Na⁺在第1天、第7天、第15天和第70天显著增加特异性结合。50 μM的GTP在第15天和第70天完全逆转了Na⁺诱导的阿扑吗啡IC50的降低,但在第7天没有。提示在第1天受体就能识别配体的立体特异性。纹状体中多巴胺受体的密度在第30天达到峰值,随后在第70天和第360天下降。此外,出生后1至2周内,Na⁺和GTP对多巴胺受体激动剂结合的调节似乎开始发挥作用。

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