Lenkei Z, Palkovits M, Corvol P, Llorens-Cortès C
INSERM U36, Chaire de Médecine Expérimentale, Collège de France, Paris, France.
Front Neuroendocrinol. 1997 Oct;18(4):383-439. doi: 10.1006/frne.1997.0155.
The discovery that all components of the renin-angiotensin system (RAS) are present in the central nervous system led investigators to postulate the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurons have been visualized in the brain. Two major pathways were described: a forebrain pathway which connects circumventricular organs to the median preoptic nucleus, paraventricular nucleus, and supraoptic nucleus, and a second pathway connecting the hypothalamus to the medulla oblongata. Blood-brain barrier deficient circumventricular organs are rich in angiotensin II receptors. By activating these receptors, circulating angiotensin II may act on central cardiovascular centers via angiotensinergic neurons, providing a link between peripheral and central angiotensin II systems. Among the effector peptides of the brain RAS, angiotensin II and angiotensin III have the same affinity for the two pharmacologically well-defined receptors: type 1 (AT1) and type 2 (AT2). When injected in the brain, these peptides increase blood pressure, water intake, and anterior and posterior pituitary hormone release and may modify memory and learning. The cloning of AT1 and AT2 receptor cDNAs has revealed that these receptors belong to the seven transmembrane domain receptor family. In rodents, two AT1 receptor subtypes, AT1A and AT1B, have been isolated. Using specific riboprobes for in situ hybridization histochemistry, recent studies mapped the distribution of AT1A, AT1B, and AT2 receptor mRNAs in the adult rat and found a predominant expression of AT1A and AT2 mRNA in the brain and of AT1B in the pituitary. Very limited overlap was found between the brain expression of AT1A and AT2 mRNAs. In several functional entities of the brain, such as the preoptic region, the hypothalamus, the olivocerebellary system, and the brainstem baroreflex arc, the colocalization of receptor mRNA, binding sites, and angiotensin immunoreactive nerve terminals suggests local synthesis and expression of angiotensin II receptors. In other areas, such as the bed nucleus of the stria terminalis, the median eminence, or certain parts of the nucleus of the solitary tract, angiotensin II receptors are likely of extrinsic origin. The neuronal expression of AT1A and AT2 receptors was demonstrated in the subfornical organ, the hypothalamus, and the lateral septum. By using double label in situ hybridization, AT1A receptor expression was localized in corticotropin releasing hormone but not in vasopressin containing neurons in the hypothalamus. The information is discussed together with functional data concerning the role of brain angiotensins, in an attempt to provide a better understanding of the physiological and functional roles of each receptor subtype.
肾素-血管紧张素系统（RAS）的所有成分均存在于中枢神经系统这一发现，促使研究人员推测存在局部脑RAS。对此的支持证据是，已在脑中观察到血管紧张素免疫反应性神经元。描述了两条主要途径：一条前脑途径，将室周器官连接至视前正中核、室旁核和视上核；另一条途径将下丘脑连接至延髓。缺乏血脑屏障的室周器官富含血管紧张素II受体。通过激活这些受体，循环中的血管紧张素II可通过血管紧张素能神经元作用于中枢心血管中枢，从而在周围和中枢血管紧张素II系统之间建立联系。在脑RAS的效应肽中，血管紧张素II和血管紧张素III对两种药理学上明确的受体具有相同的亲和力：1型（AT1）和2型（AT2）。当注入脑内时，这些肽会升高血压、增加水摄入以及促进垂体前叶和后叶激素释放，并可能改变记忆和学习。AT1和AT2受体cDNA的克隆表明，这些受体属于七跨膜结构域受体家族。在啮齿动物中，已分离出两种AT1受体亚型，即AT1A和AT1B。利用特异性核糖探针进行原位杂交组织化学，最近的研究绘制了成年大鼠中AT1A、AT1B和AT2受体mRNA的分布图，发现AT1A和AT2 mRNA在脑中主要表达，而AT1B在垂体中主要表达。发现AT1A和AT2 mRNA在脑中的表达重叠非常有限。在脑的几个功能实体中，如视前区、下丘脑、橄榄小脑系统和脑干压力反射弧，受体mRNA、结合位点和血管紧张素免疫反应性神经末梢的共定位表明血管紧张素II受体的局部合成和表达。在其他区域，如终纹床核、正中隆起或孤束核的某些部分中，血管紧张素II受体可能来源于外部。已在穹窿下器官、下丘脑和外侧隔中证实了AT1A和AT2受体的神经元表达。通过使用双重标记原位杂交，AT1A受体表达定位于下丘脑促肾上腺皮质激素释放激素神经元，但不在含血管加压素的神经元中。结合有关脑内血管紧张素作用的功能数据对这些信息进行了讨论，旨在更好地理解每种受体亚型的生理和功能作用。
