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.
Petrov
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V
Department of Molecular and Cardiovascular Research, University of Leuven, Belgium.
Amery
A
A
Lijnen
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P
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000097:blood; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000097:blood*
D010446:Peptide Fragments; D017923:Sodium-Hydrogen Exchangers; C016276:8-bromocyclic GMP; D003995:Dibutyryl Cyclic GMP; D009320:Atrial Natriuretic Factor; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase; D006152:Cyclic GMP