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.
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002415:Cats; D002838:Chromaffin System / Q000378:metabolism*; D004095:Dihydropyridines; D005260:Female; D007473:Ion Channels / Q000187:drug effects*; D017275:Isradipine; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D013237:Stereoisomerism
D002395:Catecholamines; D004095:Dihydropyridines; D007473:Ion Channels; D010069:Oxadiazoles; D011725:Pyridines; C045796:SAN 202791; D011188:Potassium; D002118:Calcium; D017275:Isradipine