Characterization of calcium antagonist receptors in highly purified porcine cardiac sarcolemma.
Drug receptors for the Ca-antagonists nitrendipine and (-)desmethoxyverapamil (D-888) were studied in porcine cardiac sarcolemma. The dihydropyridine (DHP) derivative [3H]nitrendipine binds to a single population of high affinity sites (KD = 0.44 +/- 0.10 nM, Bmax = 2.43 +/- 0.19 pmol/mg; (n = 8), whereas the phenylalkylamine derivative [3H](-)D-888 interacts with high and low affinity sites of KD = 5.1 +/- 1.4 nM and KD = 438 +/- 86 nM (n = 6) in the same membrane preparations. The antagonists tested differ also with respect to their pharmacological efficacy on cultured intact heart myocytes. The EC50 value of the negative chronotropic effect exerted by D-888 corresponds to its high affinity binding component. Nitrendipine exhibit a 200-fold lower pharmacological efficacy, as would be expected from binding data.
Haase
H
H
Central Institute of Cardiovascular Research, Academy of Sciences of GDR, Berlin.
Wallukat
G
G
Vetter
R
R
Will
H
H
D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels; D002478:Cells, Cultured; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism; D013552:Swine; D014700:Verapamil / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011978:Receptors, Nicotinic; C043184:4-desmethoxyverapamil; D009568:Nitrendipine; D014700:Verapamil