Fuxe K, Bunnemann B, Aronsson M, Tinner B, Cintra A, von Euler G, Agnati L F, Nakanishi S, Ohkubo H, Ganten D
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Clin Exp Hypertens A. 1988;10 Suppl 1:143-68. doi: 10.3109/10641968809075969.
The transmitter receptor matches and mismatches in the angiotensin (ANG) immunoreactive (IR) neuronal systems of the rat CNS have been characterized in various regions by means of ANG II immunocytochemistry and 125I-angiotensin II receptor autoradiography. By means of in situ hybridization the distribution of angiotensinogen mRNA has been mapped out and related to the distribution of ANG IR. In some areas, high densities of ANG IR nerve terminals and ANG II receptors (e.g. paraventricular hypothalamic nucleus, locus coeruleus and nucleus tractus solitarius) or high densities of ANG II receptors alone (e.g. medial geniculate body, subthalamic nucleus and superficial layer of the superior collicle) were often associated with high levels of angiotensinogen mRNA, suggesting the existence of an extracellular formation of ANG II, mediating biological responses. These results underline a role of ANG peptides in volume transmission in addition to transmitter function. Other areas, such as nuc. n. hypoglossi, practically lacking ANG IR terminals, pericarya and receptors, also contained high levels of angiotensinogen mRNA, suggesting a different role of angiotensinogen in these areas. Evidence for presynaptic (turnover changes) and post-synaptic (receptor-receptor crosstalk) interactions with CA neuronal systems has been obtained especially in cardiovascular centers. Thus, ANG II reduces in a concentration related way the affinity of 3H-paraminoclonidine binding sites in the dorsomedial medulla without influencing the Bmax value. These results indicate the existence of intramembrane interactions between ANG II and alpha 2 adrenergic receptors. Finally paraventricular but not perifornical ANG immunoreactive nerve cells costore nuclear glucocorticoid receptor IR, suggesting that some ANG neurons may be directly regulated by glucocorticoids.
通过血管紧张素II免疫细胞化学和125I-血管紧张素II受体放射自显影技术，已在大鼠中枢神经系统的各个区域对血管紧张素（ANG）免疫反应性（IR）神经元系统中的递质-受体匹配和不匹配情况进行了表征。通过原位杂交技术，已绘制出血管紧张素原mRNA的分布图，并将其与ANG IR的分布相关联。在某些区域，高密度的ANG IR神经末梢和ANG II受体（如下丘脑室旁核、蓝斑和孤束核）或仅高密度的ANG II受体（如内侧膝状体、丘脑底核和上丘表层）通常与高水平的血管紧张素原mRNA相关，这表明存在ANG II的细胞外形成，介导生物学反应。这些结果强调了ANG肽除了递质功能外，在容积传递中的作用。其他区域，如舌下神经核，实际上缺乏ANG IR终末、胞体和受体，但也含有高水平的血管紧张素原mRNA，这表明血管紧张素原在这些区域具有不同的作用。特别是在心血管中枢已获得了与CA神经元系统存在突触前（周转率变化）和突触后（受体-受体串扰）相互作用的证据。因此，ANG II以浓度相关的方式降低了背内侧延髓中3H-对氨基可乐定结合位点的亲和力，而不影响Bmax值。这些结果表明ANG II与α2肾上腺素能受体之间存在膜内相互作用。最后，室旁而非穹窿周ANG免疫反应性神经细胞共储存核糖皮质激素受体IR，这表明一些ANG神经元可能直接受糖皮质激素调节。
