Human red blood cells--an ideal model system for the action of calcium agonists and antagonists.
To characterize the pharmacological properties of the slow calcium channel of human red blood cells, we studied the action of various calcium antagonists and two agonists on the 45Ca2+-influx. The Ca2+-ejecting ATPase was inhibited by vanadate. All dihydropyridine derivatives tested showed their inhibiting or stimulating effect on the channel at concentrations attainable in vivo (nitrendipine:Ki = 2.5; Bayer K 6244:Ki 5 microM; nicardipine:Ki = 15 microM, Ks = 0.5 microM; Ciba 28 392:Ki = 20, Ks = 0.3 microM; Ki = inhibition constant, Ks = stimulation constant). Of special interest was the biphasic behaviour (stimulation and inhibition) of the calcium antagonist nicardipine and the agonist Ciba 28 392. The maximum inhibition by the phenylalkylamine derivative verapamil was obtained at much higher concentrations (250 microM; Ki = 100). These data suggest that the calcium channel of human red blood cells has pharmacological properties very similar to the channel in heart and smooth muscle cells with respect to dihydropyridine action. Therefore, human red blood cells are an ideal model to study the action of calcium agonists and antagonists.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium / Q000097:blood*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D011725:Pyridines / Q000494:pharmacology; D013268:Stimulation, Chemical; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011725:Pyridines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C040525:CGP 28392; D009568:Nitrendipine; D014700:Verapamil; D009529:Nicardipine; D009543:Nifedipine; D002118:Calcium