The EFAR research group consists of members of three departments within the Vrije Universiteit Brussel (FASC, FARC and MBFA) and was created because of the mutual interest within these groups to study the pharmacological and clinical aspects of bioactive endogenous fragments of the peptide Angiotensin II (Ang II). The renin-angiotensin system (RAS) is widely recognised as the most powerful signalling system for controlling sodium balance, body fluid volumes and arterial blood pressure. It is well established that Ang II is converted into a number of biologically active fragments. In this respect the major metabolite Ang IV produces several distinct central and vascular actions. Central actions include the increase of memory recall and learning in passive and conditional avoidance behavioural studies as well as anticonvulsive effects in models for epilepsy. With respect to renal blood flow and sodium reabsorption conflicting reports are found in literature. While some report that Ang IV increases blood flow and reduces sodium reabsorption via interaction with AT4 receptors others suggest opposite effects that may be mediated by AT1 receptors. Cellular target(s) for Ang IV, the so called AT4 receptors, have been identified as the membrane-bound metalloprotease insulin-regulated aminopeptidase (IRAP) also named placental leucine aminopeptidase (P-LAP) or oxytocinase (Otase). The EFAR research group aims to explore the potential signalling mechanisms of the IRAP/AT4 system, to evaluate the physiological relevance of its activation and/or alteration of its enzymatic activity by Ang IV. In addition it will be investigated whether the effects of Ang IV is mediated by modulation of glucose uptake since in certain cells IRAP is found to be co-localised with the insulin-sensitive glucose carrier GLUT4. The involvement of IRAP in these processes is studied by using mice in which the IRAP gene is inactivated and that are obtained in collaboration with Dr. S. Chai (Melbourne, Australia). The involvement of IRAP/AT4 in (patho)-physiological processes will also be investigated. These include epilepsy, cerebral ischemia, Alzheimer's and Parkinson's disease and recently also in inflammation. A combination of in vitro techniques (radioligand binding, enzyme activity, deoxy-glucose uptake, effector signalling pathway determination, histological techniques), in vivo animal models of brain diseases and renal function, in vivo microdialysis, behavioural studies, as well as analytical techniques (HPLC and mass spectrometry) guarantees a thorough study of fundamental/mechanistic as well as physiological/ (patho)-physiological aspects of Ang IV and of the RAS in general.