Brain natriuretic factor Augmentation of cellular cyclic GMP, activation of particulate guanylate cyclase and receptor binding

Abstract

The newly discovered peptide, brain natriuretic factor (BNF), caused a concentration-dependent increase (up to 400-fold) in intracellular cyclic GMP levels in cultured endothelial, smooth muscle and fibroblast cells. The extent of cGMP augmentation was comparable to that produced by atria1 natriuretic factor (ANF). The activity of the membrane-bound guanylate cyclase of different rat tissues and cultured cells was markedly stimulated by the peptide and the addition of ATP potentiated the stimulation. As opposed to tissue particulate guanylate cyclase, the enzyme in cell membranes was slightly more sensitive to activation by BNF than to stimulation by ANF. On bovine aortic smooth muscle (BASM) cells, specific high-affinity binding sites (B,,,u = 398 fmol/lW cells, Kd =0.52 nM) for BNF were observed for which ANF could compete with apparently equal affinity. These results suggest that activation of the cGMP pathway constitutes a common mechanism of action for both BNF and ANF.

Adenine nucleotides decrease the apparentKmof endogenous natriuretic peptide receptors for GTP

“…Subsequently, addition of exogenous ATP to the reaction was reported to further increase ANP-dependent guanylyl cyclase activity (8,24,41). Similar stimulatory effects of ATP were reported for the intestinal and retinal guanylyl cyclases as well (17,42,44).…”

Comparison of Plasma Levels of Mature Adrenomedullin and Natriuretic Peptide as Markers of Cardiac Function in Hemodialysis Patients with Coronary Artery Disease

“…It has been suggested that, like ANP and BNP, volume overload may be a stimulus for synthesis and secretion of AM by vascular endothelial [21]and smooth muscle cells [22], despite the differences in their intracellular signaling systems [9, 23, 24, 25, 26]. In addition, it has been reported that the failing ventricular myocardium itself may be a source of increased AM production [27, 28].…”

Receptors for atrial natriuretic peptide are decreased in the kidney of rats with streptozotocin-induced diabetes mellitus.

“…cGMP PDE activity was assayed according to the method of Torres et al (27). Cytosolic fractions of IMCD cell homogenates, collected as described (10)(11)(12)(13)(14)(15) Values are means±SEM. Significant difference versus control rats is indicated by * P < 0.01, and * P < 0.05.…”

“…ANPR-C, also known as the ANP clearance receptor, does not signal through activation of guanylyl cyclase, but may serve as a clearance receptor for natriuretic peptides; it may also function through intermediate guanine nucleotide regulatory proteins to inhibit adenylyl cyclase (11). While ANPR-A and ANPR-B have rather strict structural requirements for ligand binding (12)(13)(14)(15), ANPR-C has less rigorous structural requirements and binds the internally deleted analogues of ANP (c-ANP) (12,(16)(17)(18), compounds which do not activate the membrane guanylate cyclase.…”