The effects of harmaline on sodium transport in human erythrocytes: evidence in favor of action at interior sodium-sensitive sites.

The effects of the hallucinogen, harmaline (HME), and its congeners on human red blood cell (RBC) transport were studied. HME reduced sodium efflux by 70% at maximum inhibitory concentrations (6-8 mM). It acted upon the ouabain-sensitive component of sodium efflux since it exerted no inhibitory actions in the presence of ouabain. Several lines of evidence suggested that HME exerted its inhibitory effect at intracellular sodium-sensitive sites. The percent inhibition of Na efflux by 0.1 mM HME was unaffected by increasing extracellular potassium from 10 to 100 mM. When HME was incorporated into RBC ghosts by reversible hemolysis, the degree of inhibition of sodium efflux was comparable to that found with ouabain outside the red cells and was always greater than the inhibition produced with HME outside cells. HME increased membrane permeability to sodium, as shown by enhanced sodium influx into RBC and at concentrations of 10 mM caused rapid increments of intracellular sodium and decrements of intracellular potassium. We conclude that the harmala alkaloids inhibit the active Na-K transport system in human RBCs through their effects on sodium-sensitive transport sites on the interior membrane surface.