Atrial natriuretic peptide II and III stimulation of Na+/H+ exchange in human erythrocytes.
In the present study we investigated in human red blood cells, the effect of the atrial natriuretic polypeptide fragments ANPI, ANPII, ANPII, alpha-ANP and des-Ser5,Ser6-ANPIII, in a combination range of 1 pM to 100 nM, upon the Na+/H+ exchange. We have shown that ANPII and ANPIII stimulate the erythrocyte Na+/H+ exchange while alpha-ANP, ANPI and des-Ser5,Ser6-ANPIII have no effect. In the present study, we also tested the hypothesis that ANPIII stimulation of erythrocyte Na+/H+ exchange occurs via an increase in cGMP levels. When the quinolinedione, 6-anilo-5,8-quinolinedione (LY83583) (10 microM), was used to block formation of cGMP in human red blood cells, it was found that basal and ANPIII stimulated Na+/H+ exchange were inhibited. The cGMP analogs, dibutyryl-cGMP and 8-Br-cGMP, also increase the erythrocyte Na+/H+ exchange. The 8-Br-cGMP-stimulated Na+/H+ exchange was not affected by 2-0-propoxyphenyl-8-azapurine-6-one (MB22948), an inhibitor of cGMP phosphodiesterase MB22948 alone also increased levels of Na+/H+ exchange. The ANPIII stimulated Na+/H+ exchange was also accompanied by an elevation of the intracellular cGMP level. Since inhibition of cGMp formation blocks ANP111-stimulated Na+/H+ exchange and inhibition of cGMP breakdown enhances it, we conclude that ANP111 stimulation of Na+/H+ exchange in human red blood cells is mediated via increases in intracellular cGMP levels.
Lijnen
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P
Department of Molecular and Cardiovascular Research, University of Leuven, Belgium.
Petrov
V
V
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000634:Aminoquinolines / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects* / Q000378:metabolism
D000634:Aminoquinolines; D010446:Peptide Fragments; D011688:Purinones; D017923:Sodium-Hydrogen Exchangers; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; C041715:6-anilino-5,8-quinolinedione; D000242:Cyclic AMP; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase; C011145:zaprinast; D006152:Cyclic GMP