Inhibition of the Na+/K+ cotransport system by cyclic AMP and intracellular Ca2+ in human red cells.
Human erythrocytes are able to incorporate cyclic AMP (cAMP) in amounts larger than those required to saturate cAMP-dependent protein kinase. In contrast to previous observations in avian red blood cells in which cAMP stimulates the Na+/K+ cotransport system, we demonstrate that cAMP inhibits this system in human erythrocytes. The cotransport inhibition is enhanced by addition of phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine to the incubation medium. The cAMP concentration giving half-maximal cotransport inhibition showed a wide variation among different individuals (from 0.1 to 5 mM external cAMP concentration). In contrast to cAMP, cyclic GMP showed little effect on the cotransport system. Ca2+ introduced into the cell interior was an inhibitor of the Na+/K+ cotransport system. These results suggest that in human cells in which endogeneous levels of cAMP and Ca2+ are modulated by hormones, the Na+/K+ cotransport system may be under hormonal regulation.
D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000097:blood* / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood* / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D011188:Potassium / Q000097:blood*; D011941:Receptors, Adrenergic / Q000187:drug effects; D012964:Sodium / Q000097:blood*
D011941:Receptors, Adrenergic; D012964:Sodium; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium