fig1

Figure 1. The biologically active ligands (bold), enzymes, and receptor proteins of the angiotensinogen-renin-angiotensin pathway that regulate angiotensin-based physiologies and behaviors. Angiotensinogen is a precursor protein consisting of 255 amino acids. Angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) binds at the AT₁ receptor subtype and mediates systemic blood pressure, body water/electrolyte balance and influences cerebral blood flow, cerebroprotection, seizure, stress and depression. Angiotensin III (Arg-Val-Tyr-Ile-His-Pro-Phe) binds at the AT₁ but primarily at the AT₂ receptor subtype and modulates cell proliferation, cell differentiation, and apoptosis. This system also encourages some cellular regenerative processes and opposes most actions initiated by the angiotensin II/AT₁ receptor system. Angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) and Angiotensin (3-7: Val-Tyr-Ile-His-Pro) bind at HGF thus stimulating dimerization a prerequisite to autophosphorylation of the Met receptor. This system mediates neuroprotection, synaptogenesis, cerebral blood flow, long-term potentiation and memory consolidation and retrieval. Both that AT₁ and AT₂ receptor subtypes are 7-transmembrane domain G-protein coupled receptors with molecular weights of 40-42 kDa. The Met receptor is a dimer as seen in growth factors, with a molecular weight of 160-190 kDa. ACE: angiotensin converting enzyme; AP-A: aminopeptidase A; AP-N: aminopeptidase N; Carb-P: carboxypeptidases P; HGF: hepatocyte growth factor; PO: propyl oligopeptidase