NICARDIPINE ENANTIOMERS INHIBIT CALCIUM AND OUTWARD CURRENTS IN RAT PARS-INTERMEDIA CELLS

The whole-cell patch clamp technique was used to investigate the effec t of the dihydropyridine antagonist nicardipine and its two enantiomer s on calcium and outward currents in rat pars intermedia cells. Inward voltage-activated calcium currents as well as outward currents were b locked by nicardipines (enantiomers and racemic substance). We found a highly significant correlation between the blockage of voltage-activa ted currents and outward currents, indicating an association between r ecorded currents. Therefore, the inhibitory effect of nicardipines was measured as outward current inhibition. The effects of (-) and (+) en antiomers as well as the racemic nicardipine were concentration-depend ent. The (+)-enantiomer was the least potent with an ED(50) of 3.8 +/- 1.2 mu M, while the (-)-enantiomer inhibited currents with an ED(50) of 0.7 +/- 0.1 mu M. Racemic nicardipine blocked currents with an ED(5 0) of 2.2 +/- 0.6 mu M.