SUBFORNICAL ORGAN - DIPSOGENIC SITE OF ACTION OF ANGIOTENSIN-II
SUBFORNICAL ORGAN - DIPSOGENIC SITE OF ACTION OF ANGIOTENSIN-II
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DOI：
10.1126/science.663664
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发表时间：
1978-01-01
期刊：
影响因子：
56.9
通讯作者：
ROUTTENBERG, A
中科院分区：
文献类型：
--
作者：
SIMPSON, JB;ROUTTENBERG, A
几年前，有人提出颅内注射物质可能不会在注射部位起作用，但事实上可能会通过心室 (1) 或脑脉管系统 (2) 扩散，然后在某个远处的部位起作用。我们已经表明，促性剂传播的一个目标是穹窿下器官 (SFO)(3)，这一观点得到了部分支持，因为局部 SFO 损伤减少了下丘脑内血管紧张素 II (All)(4) 诱导的饮酒。 Buggy 等人 (5) 的报告将我们的观点归因于“穹窿下器官 (SFO) 含有血管紧张素诱导饮酒的唯一受体”(5，第 72 页)。相反，我们指出，“很容易推测循环血管紧张素 II 的中央促性受体位于 SFO 内”（4，第 1174 页）。尽管他们对我们立场的描述不准确，但我们相信，人们对确定 AII 的中心行动地点有足够的兴趣，值得讨论他们的发现和解释。我们首先考虑 Buggy 等人 (5) 造成的 SFO 损伤，他们报告说，颅内 AII 诱发的饮酒在 SFO 被破坏 70% 至 100% 后恢复了。 SFO 由喙区、中央区和尾区组成 (6)，每个区都具有超微结构可识别的神经元周核。由于没有提供病变程度的详细描述，因此很难确定用于表示 SFO 病变 (5) 的“70% 至 100% 破坏”指的是什么。也很难确定哪些邻近组织（例如脉络丛基底层）受到这些病变的损害。 SFO 部分的保留可能是这些作者观察到的损伤后饮酒的原因，这一点之前已指出 (4, 7)。在我们的研究 (4) 中，动物根据神经损伤而不是行为表现 (5) 进行分类。我们发现，在所有诱导饮酒中，动物遭受不彻底 SFO 损伤的情况并没有减少 (4, 7)。 SFO 损伤后 AII 饮水不存在永久性缺陷 (5) 可能部分归因于产生或评估损伤的方法，或两者兼而有之 (8)。有人建议 (5) 颅内注射 All 的同侧室间孔的阻断，而不是消融 SFO，产生了 SFO 损伤引起的饮水缺陷。虽然如果同侧室间孔完全闭塞，饮酒量可能会减少，Buggy 等人。尚未证明椎间孔完全闭塞。事实上，在他们的放射性示踪实验中，堵塞并不完全 (5)。因此，与恢复的病变动物相比，100 或 500 ng 脑室内剂量的 All 中有 11% 可能通过脑室扩散进入蛛网膜下腔 (9)。侧脑室 AII 诱发饮酒的阈值低于 All (10) 的 1 ng。由于这些作者根据诱导饮酒的减少而不是根据 SFO 损伤的程度对动物进行分类，因此心室闭塞与 SFO 损伤对所有饮酒中观察到的缺陷的相对贡献仍然不确定。
Several years ago it was proposed that intracranially injected material may not act at the site of injection but may, in fact, spread via the ventricles (1) or the cerebral vasculature (2) to then act at some distant locus. We have indicated that one target for the spread of dipsogenic agents is the subfornical organ (SFO)(3), a position supported in part because localized SFO lesions reduced drinking induced by intrahypothalamic angiotensin II (All)(4). The report by Buggy et al.(5) attributed to us the view that" the subfornical organ (SFO) con-tains the exclusive receptors for angio-tensin-induced drinking"(5, p. 72). Rather, we stated," It is tempting to speculate that the central dipsogenic re-ceptors for circulating angiotensin II are within the SFO"(4, p. 1174). Despite their inaccurate portrayal of our posi-tion, we believe that there is sufficient interest in determining central AII sites of action to warrant discussion of their findings and interpretations. We consider first the SFO lesions made by Buggy et al.(5), who report that intracranial AII-induced drinking recov-ered after 70to 100 percent destruction of SFO. The SFO consists of rostral, central, and caudal zones (6), each of which possesses ultrastructurally identifiable neuronal perikarya. Because de-tailed description of the extent of the lesions is not provided, it is difficult to de-termine to what" 70 to 100 percent destruction," used to denote SFO lesions (5), refers. It is also difficult to ascertain what adjacent tissues (for example, cho-roid plexus basal laminae) were damaged by these lesions. Sparing of portions of the SFO might be responsible for the drinking after lesionsobserved by these authors, a point previously indicated (4, 7). In our study (4), animals were classified in terms of neural damage rather than in terms of behavioralperformance (5). We have found that animals sustaining less than thorough SFO lesions are not reduced inAll-induced drinking (4, 7). The absence of permanent deficits in AII drinking after SFO lesions (5) may be attributable, in part, to the methods of producing or of evaluating lesions, or both (8).It was suggested (5) that blockade of the interventricular foramen ipsilateral to intracranialinjections of All, and not ablation of the SFO, produced deficits in elicited drinking consequentto SFO lesions. While reduced drinking could occur if the ipsilateral interventricular fora-men were completely occluded, Buggy et al. have not demonstrated the com-plete occlusion of the foramen. In their radioactive tracing experiments, in fact, the blockage was not complete (5). Thus, as compared to recovered lesioned animals, 11 percent of the 100-or 500-ng intraventricular dose of All passed into subarachnoid space, presumably via ventricular diffusion (9). The threshold for lateral ventricular AII-induced drinking is less than 1 ng of All (10). Since these authors classified animals in terms of the reduction in elicited drinking and not in terms of extent of SFO damage, the relative contribution of ventricular occlusion versus SFO damage to the observed deficits in All drinking remains uncertain.