Hormonal modulation of ionic permeability in human red blood cells

It has previously been reported that both exogenous adenosine cAMP analogs and forskolin-induced elevations in intracellular cAMP concentrations selective increase relative ionic chloride permeability in normal human red blood cells (RBC). A similar selectively increase in relative ionic chloride permeability was observed in untreated uremic subjects in whom endogenous RBC cAMP concentrations are chronically elevated. To detect which hormones might modulate RBC cAMP and ionic permeabilities, RBC were exposed to norepinephrine, epinephrine, and parathyroid hormone. Thereafter, RBC cAMP concentrations were measured by RIA and relative ionic permeabilities were determined in human RBC ghosts with the potential sensitive fluorescent probe diS-C3-(5). In ghosts prepared from normal RBC, norepinephrine and epinephrine significantly increased intracellular cAMP concentrations; in these ghosts, relative ionic chloride permeability (permeability of chloride/permeability of potassium (PCI/PK)), but not PNa/PK (permeability of sodium/permeability of potassium), was significantly increased. In contrast, exposure to parathyroid hormone did not affect either cAMP concentrations or relative ionic permeabilities. These results are consistent with the presence of adrenergic receptors and the absence of parathyroid hormone receptors in RBC. These studies demonstrate that hormonally induced changes in cAMP can modulate RBC relative ionic chloride permeability and suggest that, in uremic RBC, increased relative ionic chloride permeability could be consequent to elevated plasma levels of epinephrine or norepinephrine.