Biochemical, Structural and Pathophysiological Aspects of Prorenin and (Pro)renin Receptor

Abstract

Our knowledge of understanding the complex role of renin angiotensin system (RAS) or RA system in human physiology has been widened for more than 100 years and it is rapidly increasing day-by-day. Over the last two decades discoveries of angiotensin converting enzyme 2 (ACE 2), putative receptor for angiotensin (Allen et al., 2006; Aronsson et al. 1988; Bickerton & Buckley, 1961; Cooper et al., 1996; Deschepper et al., 1986; Dzau et al., 1986; Epstein et al., 1970), and (pro)renin receptor have laid the foundation of many new hypotheses in the context of their biochemical actions, physiological effects and activation of second messenger pathways. Thus, scientists have started to reconsider the complex biochemistry and physiology of RAS. The primary and main role of this system is to regulate homeostasis of body fluid that ultimately maintains the blood pressure (Kobori et al., 2006; Oparil & Haber, 1974a; Oparil & Haber; 1974b). This system catalyzes a liver product, angiotensinogen, to generate a small decapeptide, angiotensin-I (Ang-I). Angiotensin converting enzyme (ACE), thus, converts Ang-I into octapeptide, angiotensin-II (Ang-II). Ang-II acts directly within the central nervous system to increase blood pressure (Bickerton & Buckley, 1961). Injection of purified Ang-II peptide around the hypothalamus in rat brain stimulated thriving drinking response (Epstein et al., 1970). The physiological actions of the most potent hormone peptide are mediated via G-protein coupled angiotensin II type 1 (AT1) and angiotensin II type 2 (AT2) receptors. Ang-II facilitates vasoconstriction, cell proliferation, cell hypertrophy, anti-natriuresis, fibrosis, atherosclerosis using AT1 (Ito et al., 1995) while, via AT2 receptor, the peptide elicits vasodilation, anti-proliferation, antihypertrophy, anti-fibrosis, anti-thrombosis, anti-angiogenesis (Siragy & Carey, 1997; Goto et al., 1997; Gross et al., 2000). The classical renin angiotensin system with the generation of different peptides and their physiological effects has been presented in Figure 1.