Atrial Natriuretic Peptide

Literature References: Peptide hormone involved in the regulation of salt and fluid balance and blood pressure homeostasis. Endogenous antagonist of the renin angiotensin aldosterone system; physiological effects include vasodilation, natriuresis and diuresis. Produced primarily by the cardiac atrium; also identified in the lung, brain and kidney. Synthesized as a species dependent, 149-153 residue precursor (preproANP) which is cleaved to produce a 126 residue prohormone that is stored in myocyte granules. The major circulating form, known as a-ANP, is a 28 amino acid peptide derived from the carboxy terminus of the prohormone. The amino acid sequence is highly conserved across species. Several bioactive forms of varying length have been identified. Removal of ANP from circulation is effected by clearance receptors and by neutral endopeptidase, also known as atriopeptidase or enkephalinase, that cleaves the disulfide bond required for activity. Demonstration of physiological effect: A. J. de Bold et al., Life Sci. 28, 89 (1981). Purification and amino acid sequence of rat ANP peptides: T. G. Flynn et al., Biochem. Biophys. Res. Commun. 117, 859 (1983); of human: K. Kangawa, H. Matsuo, ibid. 118, 131 (1984). Synthesis of bioactive forms of ANP: N. G. Seidah et al., Proc. Natl. Acad. Sci. USA 81, 2640 (1984); S. A. Atlas et al., Nature 309, 717 (1984). Series of articles on cloning and sequence analysis: ibid. 719-726. Identification of storage form: K. Kangawa et al., ibid. 312, 152 (1984); of major circulating form: A. Miyata et al., Biochem. Biophys. Res. Commun. 129, 248 (1985); D. Schwartz et al., Science 229, 397 (1985). Clinical pharmacology of synthetic peptide: A. M. Richards et al., Lancet 1, 545 (1985). Identification of clearance receptors: T. Maack et al., Science 238, 675 (1987). Role of endopeptidase to inactivate ANP: A. J. Kenny, S. L. Stephenson, FEBS Lett. 232, 1 (1988). Determn in plasma by RIA: L. M. Burrell et al., J. Immunoassay 11, 159 (1990). Review of early literature: A. J. de Bold, Science 230, 767-770 (1985); of physiological effects: P. Needleman, J. E. Greenwald, N. Engl. J. Med. 314, 828-834 (1986); J. D. Baxter et al., Biotechnology 6, 529-546 (1988). Review of biosynthesis, release and metabolism: H. Ruskoaho, Pharmacol. Rev. 44, 479-602 (1992). Review of clinical pharmacology and therapeutic potential: A. Deutsch et al., J. Clin. Pharmacol. 34, 1133-1147 (1994). Role in lung physiology and pathology: T. Perreault, J. Gutkowska, Am. J. Respir. Crit. Care Med. 151, 226-242 (1995).