The ANF-RGC gene motif (669)WTAPELL(675) is vital for blood pressure regulation: biochemical mechanism.

ANF-RGC is the prototype membrane guanylate cyclase, both the receptor and the signal transducer of the hormones ANF and BNP. After binding them at the extracellular domain, it, at its intracellular domain, signals activation of the C-terminal catalytic module and accelerates production of the second messenger, cyclic GMP. This, in turn, controls the physiological processes of blood pressure, cardiovascular function, fluid secretion, and others: metabolic syndrome, obesity, and apoptosis. The biochemical mechanism by which this single molecule controls these diverse processes, explicitly blood pressure regulation, is the subject of this study. In line with the concept that the structural modules of ANF-RGC are designed to respond to more than one yet distinctive signals, the study demonstrates the construction of a novel ANF-RGC-In-gene-(669)WTAPELL(675) mouse model. Through this model, the study establishes that (669)WTAPELL(675) is a vital ANF signal transducer motif of the guanylate cyclase. Its striking physiological features linked with their biochemistry are the following. (1) It controls the hormonally dependent cyclic GMP production in the kidney and the adrenal gland. Its deletion causes (2) hypertension and (3) cardiac hypertrophy. (4) These mice show higher levels of the plasma aldosterone. For the first time, a mere seven-amino acid-encoded motif of the mouse gene has been directly linked with the physiological control of blood pressure regulation, a detailed biochemistry of this linkage has been established, and a model for this linkage has been described.