ROLE OF CYCLIC-GMP IN ATRIAL-NATRIURETIC-PEPTIDE STIMULATION OF ERYTHROCYTE NA+/H+ EXCHANGE

Human atrial natriuretic peptide (ANP) fragments ANP-(127-150) or ANP-III and ANP-(127-149) or ANP-II activate Na+/H+ exchange in human erythrocytes at concentrations as low as 1 pM. Both ANP-(127-147) or ANP-I and ANP-(129-150) or des-Ser5, Ser6-ANP-III have no effect on erythrocyte Na+/H+ exchange. ANP-III also produces a time-dependent increase of intraerythrocyte guanosine 3',5'-phosphate (cGMP) concentration. M&B 22,948, a specific inhibitor of cGMP phosphodiesterase, increases Na+/H+ exchange and the intracellular concentration of cGMP. Both 8-bromoguanosine 3',5'-phosphate (8-Br-cGMP) and dibutyryl-cGMP mimic the effect of ANP-III on erythrocyte Na+/H+ exchange. Our data suggest that human erythrocytes possess guanylate-cyclase activity stimulated by ANP-III and that activation of Na+/H+ exchange by this peptide is mediated by cGMP. Human erythrocytes display a high degree of sensitivity to ANP-III or ANP-II and a specificity for ANP-fragment structures just as cells with established ANP-specific receptors.