POSTNATAL-DEVELOPMENT OF STRIATAL DOPAMINE FUNCTION .1. AN EXAMINATION OF D1 AND D2 RECEPTORS, ADENYLATE-CYCLASE REGULATION AND PRESYNAPTIC DOPAMINE MARKERS
POSTNATAL-DEVELOPMENT OF STRIATAL DOPAMINE FUNCTION .1. AN EXAMINATION OF D1 AND D2 RECEPTORS, ADENYLATE-CYCLASE REGULATION AND PRESYNAPTIC DOPAMINE MARKERS
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DOI：
10.1016/0165-3806(90)90244-s
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发表时间：
1990-03-01
期刊：
影响因子：
--
通讯作者：
BENNETT, JP
中科院分区：
文献类型：
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作者：
BROADDUS, WC;BENNETT, JP
我们对出生后1 - 7周的大鼠纹状体均质液中D1和D2多巴胺（DA）受体位点、与DA受体功能偶联的腺苷酸环化酶（AC）酶活性、鸟嘌呤核苷酸结合位点和DA末端功能的突触前标记物进行了表征。每单位膜蛋白表达的D1受体密度在这段发育期间没有增加，而每毫克膜蛋白的最大da刺激AC活性增加了50-100%。D1激动剂对D1受体位点的亲和力在7周龄时翻倍，但在发育过程中被鸟嘌呤核苷酸持续降低。鸟嘌呤核苷酸刺激AC在3周龄后形成双相剂量-反应曲线。在出生后2至4周，AC催化成分活性迅速增加，表现为福斯克林或锰离子在鸟嘌呤核苷酸和DA存在下刺激AC的能力。可逆[3H]GppNHp （guananyldiphosphonatiimidophospate）与纹状体均质物的结合依赖于Mg2+，被Ca2+和GppNHp类似物抑制，并且在D1位点上发生约300倍的过量。通过[3H]mazindol结合检测，多巴胺能功能的突触前标记物表明，组织DA水平增加了7倍，DA周转量减少了2倍，DA摄取位点密度没有明显变化。D1和D2 DA受体的亚组分具有不同的出生后发育特征。纹状体D1位点在发育过程中变化不明显，但D2受体和GTP对AC的抑制分别在3-4周龄时增加并出现，同时纹状体大量基质神经受DA末梢支配。
We have characterized the postnatal development from 1 to 7 weeks after birth in rat striatal homogenates of D1 and D2 dopamine (DA) receptor sites, adenylate cyclase (AC) enzyme activity coupled to DA receptor function, guanine nucleotide binding sites and presynaptic markers of DA terminal function. D1 receptor density, expressed per unit of membrane protein, does not increase over this developmental interval, while maximum DA-stimulated AC activity per mg membrane protein increases 50-100%. D1 agonist affinity for D1 receptor sites doubles by 7 weeks of age but is consistently reduced by guanine nucleotide during development. Guanine nucleotide stimulation of AC develops a biphasic dose-response curve after 3 weeks of age. Between 2 and 4 weeks postnatal age there is a rapid increase in AC catalytic component activity as manifested by the capacity of forskolin or manganese ion to stimulate AC in presence of guanine nucleotide and DA. Reversible [3H]GppNHp (guanyldiphosphonateimidophosphate) binding to striatal homogenates is dependent on Mg2+, inhibited by Ca2+ and GppNHp analogues, and occurs in about a 300-fold excess over D1 sites. Presynaptic markers of dopaminergic function indicate a 7-fold increase in tissue DA levels, a 2-fold reduction in DA turnover and no apparent change in density of DA uptake sites, assayed by [3H]mazindol binding. Subcomponents of D1 and D2 DA receptors have distinct postnatal developmental profiles. Striatal D1 sites do not change significantly during development, but D2 receptors and GTP inhibition of AC increase and appear, respectively, at 3-4 weeks of age, at the same time as the massive matrix innervation of striatum by DA terminals.