EFFECT OF PARATHYROID-HORMONE ON OSMOTIC FRAGILITY OF HUMAN-ERYTHROCYTES

The survival of erythrocytes (RBC) is shortened in uremia, and it has been shown that Ca influx into RBC evoked crenation and increased their rigidity. The high blood levels of parathryoid hormone (PTH) may augment entry of Ca into RBC and hence affect their integrity. The effect of PTH on osmotic fragility of human RBC was examined and the mechanisms through which PTH interacts with RBC were investigated. Both the N-terminal (1-34) PTH and the intact (1-84) PTH, but not the C-terminal (53-84) PTH, produced significant increases in osmotic fragility. This effect was abolished by prior inactivation of the hormone. There was a dose-response relationship between both moieties of PTH and the increase in osmotic fragility. This action of PTH required Ca, was mimicked by Ca ionophore [calcimycin], and was partially blocked by verapamil. PTH caused significant influx of 45Ca into RBC, which was not associated with K leak. The hormone did not affect water content of RBC. Scanning electron microscopy revealed that the incubation of RBC with PTH was associated with the appearance of membrane filamentous extensions, which anchor RBC together. Inhibition of glycolytic activity of RBC with NaF or inhibition of Na-K-activated ATPase with ouabain did not abolish the effect of PTH on osmotic fragility. PTH did not stimulate RBC Na-K-activated ATPase or Mg-dependent ATPase but caused marked and significant stimulation of Ca-activated ATPase. The basal activity of the RBC adenylate cyclase was low and PTH produced only a modest stimulation of this enzyme. Both cAMP and dibutyryl cAMP had no effect on osmotic fragility. Evidently, the RBC is a target organ for PTH, the hormone increases osmotic fragility of RBC, and this effect of PTH is due to enhanced Ca entry into RBC. The increased Ca influx may affect the spectrin-actin of the cytoskeletal network of the RBC and may alter the stability and integrity of the cell membrane. This action of PTH on the RBC could be at least in part, responsible for the shortened survival of RBC in uremia, and assign a new role for PTH in the pathogenesis of the anemia of uremia.