Dihydropyridine chirality at the chromaffin cell calcium channel

The racemic mixture of the dihydropyridine PN200-110 (Sandoz) inhibits K+-evoked catecholamine release from cat adrenal glands with an IC50 of 4.1 nM; IC50's for (+)- and (-)-PN200-110 were 0.84 and 45.8 nM, respectively. While the (+)-enantiomer of the dihydropyridine Sandoz 202-791 potentiated secretion (EC50 = 100 nM), the (-)-enantiomer behaved as a potent inhibitor (IC50 = 10 nM). Since K+-evoked 45Ca-uptake was also potently inhibited by (+)-PN200-110, it seems that the chromaffin cell dihydropyridine receptor is associated to the voltage-dependent Ca-channel and that it exhibits an exquisite stereoselectivity.