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通过光学显微镜放射自显影术对大鼠脑中血管加压素和催产素高亲和力结合位点进行定位及药理学特性研究

Localization and pharmacological characterization of high affinity binding sites for vasopressin and oxytocin in the rat brain by light microscopic autoradiography.

作者信息

Tribollet E, Barberis C, Jard S, Dubois-Dauphin M, Dreifuss J J

机构信息

Department of Physiology, University Medical Center, Geneva, Switzerland.

出版信息

Brain Res. 1988 Feb 23;442(1):105-18. doi: 10.1016/0006-8993(88)91437-0.

DOI:10.1016/0006-8993(88)91437-0
PMID:2834008
Abstract

Sites which bind tritiated vasopressin (AVP) with high affinity were detected in the brain of male, adult rats, by light microscopic autoradiography. Their anatomical localization differed markedly from that of high affinity binding sites for tritiated oxytocin (OT) determined in the same animal. Co-labelling was minimized by using low concentrations of [3H]AVP and [3H]OT. Binding of the former occurred predominantly in several structures of the limbic system (septum, amygdala, bed nucleus of the stria terminalis, accumbens nucleus), in two hypothalamic nuclei (suprachiasmatic and dorsal tuber) and in the area of the nucleus of the solitary tract. Binding of OT was evidenced in the olfactory tubercle, the ventromedial hypothalamic nucleus, the central amygdaloid nucleus and the ventral hippocampus. The ligand specificity of the binding sites was assessed in competition experiments. Synthetic structural analogues were used, allowing to discriminate OT receptors (OH[Thr4,Gly7]OT) from V2 receptors (dDAVP and d[Tyr(Me)2]VDAVP), V1 receptors ([Phe2,Orn8]VT) and V1b receptors (desGly9d(CH2)5AVP). Our main conclusions are, firstly, that AVP and OT binding sites can be readily distinguished, and that there is virtually no overlap in their distribution in the rat brain. Second, we showed that the sites which bind AVP with high affinity in the brain are V1 receptors, different both from the renal V2 receptors and from the anterior pituitary V1b receptors. Our results support the conjecture that AVP and OT play a role in interneuronal communication in the brain.

摘要

通过光学显微镜放射自显影术,在成年雄性大鼠的大脑中检测到了与氚标记血管加压素(AVP)具有高亲和力的位点。它们的解剖定位与在同一动物中测定的氚标记催产素(OT)高亲和力结合位点明显不同。通过使用低浓度的[3H]AVP和[3H]OT,共标记被降至最低。前者的结合主要发生在边缘系统的几个结构(隔区、杏仁核、终纹床核、伏隔核)、两个下丘脑核(视交叉上核和背侧结节)以及孤束核区域。OT的结合在嗅结节、下丘脑腹内侧核、中央杏仁核和腹侧海马中得到证实。在竞争实验中评估了结合位点的配体特异性。使用了合成结构类似物,从而能够区分OT受体(OH[Thr4,Gly7]OT)与V2受体(dDAVP和d[Tyr(Me)2]VDAVP)、V1受体([Phe2,Orn8]VT)和V1b受体(desGly9d(CH2)5AVP)。我们的主要结论是,首先,AVP和OT结合位点可以很容易地被区分,并且它们在大鼠脑中的分布几乎没有重叠。其次,我们表明大脑中与AVP具有高亲和力结合的位点是V1受体,与肾V2受体和垂体前叶V1b受体均不同。我们的结果支持了AVP和OT在大脑神经元间通讯中起作用的推测。

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