The neuronal role of angiotensin II in thirst, sodium appetite, cognition and memory

Within the past two decades, a great deal has been learnt about the renin-angiotensin system in the brain. The renin-angiotensin system is one of the best-studied enzyme-neuropeptide systems in the brain. The diversity of localization of this peptide throughout the brain has implied a variety of potential functions. Besides its classical role in the regulation of blood pressure and body-fluid homeostasis, it has more subtle functions involving complex mechanisms such as learning and memory. The profound effects on behaviour produced by angiotensin are of broad interest to neuroscientists. The mechanisms of action differ depending on whether angiotensin is locally synthesized and whether regulation is governed by neural or metabolic inputs impinging on the neurones. Its central action is mediated through peptidergic receptors present on neurones. The description of the receptor subtypes AT1 and AT2 for angiotensin II and the development of non-peptidic specific angiotensin receptor subtype antagonists have opened a new area in this field of research. The AT1 site, which preferentially binds to angiotensin II and angiotensin III, appears to mediate the classical angiotensin functions concerned with maintenance of blood pressure and body-fluid control. In addition, most of the behavioural effects described so far are linked with AT1, although so-called psychotropic effects are presumed to be mediated by receptor systems other than the known specific angiotensin receptors. In fact, evidence for the existence of such receptors with high-affinity binding has been reported. The central action of angiotensin II mediated by AT2 is as yet unclear. Most reports concerning this receptor subtype suggest a role in differentiation and development, since the number of binding sites is higher in fetal and young rats than in adults. Furthermore, the neuronal effect of angiotensin II in the inferior olivary nucleus which is blocked specifically by AT2 antagonists suggests an involvement in motor control. Over the next few years we should find answers to many of the questions currently unanswered about angiotensin function and, given the rapid progress in research on this neuropeptide, it may serve as a model for the action of peptides on neuronal function in general.