FIGURE 15-10 Structural organization of atrial natriuretic peptides and their receptors. (A) Structural homology of the A, B, and C types of human ANP. In the 17-membered ring, amino acids that are identical are shown as open circles. Abbreviations: ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; CNP, C-type natriuretic peptide. Modified with permission from Sudoh et al. (1990). (B) Schematic representation of receptor classes for human ANP. Note: The terminology for designation of the receptors ANPR-A, ANPR-B, and ANPR-C does not coincide with the terminology for their preferred ligands ANP, BNP, and CNP. The solid lines connect the respective natriuretic peptide with its preferred receptor(s). TM: transmembrane region of the receptor. Modified with permission from Koller, J. K., Lowe, D. G., Bennett G. L. et al. (1991). Selective activation of the B-natriuretic peptide receptor by c-type natriuretic peptide (CNP). Science 252. 120-123.
2. Chemistry, Biosynthesis, and Secretion
Three isoforms of endothelin have been identified; they are termed endothelins 1, 2, and 3 (ET-1, ET-2, and ET-3). The structures of the endothelins and their corresponding proendothelins are presented in Figure
15-12. Three separate ET genes have been identified; each codes for a separate and distinct endothelin. After transcription of the ET-1 gene, the mature mRNA codes for a prepro-ET-1 of 203 amino acids. Removal of the amino-terminal 20-amino-acid leader sequence generates a 183-amino acid protein that is an intermediate
FIGURE 15-11 Schematic diagram of the ANP hormonal system. An elevated vascular volume results in cleavage and release of atriopeptin, which acts on the kidney (glomeruli and papilla) to increase the glomerular filtration rate (GFR) so as to increase renal blood flow (RBF), increase urine volume (UV) and Na+ excretion (UNa), and decrease plasma renin activity. Natriuresis and diuresis are also enhanced by the suppression of aldosterone production and its actions and by the release from the posterior pituitary of arginine vasopressin (AVP). Diminution of vascular volume provides a negative feedback signal that suppresses circulating levels of atriopeptin. Modified from Needleman, P., and Greenwald, J. E. (1986). Atriopeptin: A cardiac hormone intimately involved in fluid, electrolyte, and blood pressure homeostasis. New Engl. J. Med. 314, 828-834.
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