Does [3H]nifedipine label the calcium channel in rabbit myocardium?
The ionic and drug specificities of the [3H]nifedipine binding site in rabbit cardiac homogenates were investigated. Divalent cations inhibited specific [3H]nifedipine binding in the potency order: Ni+2 greater than Ca+2 greater than or equal to Mg+2. Monovalent cations did not affect binding. The inorganic calcium entry blocker La+3 (IC50 = 1.1 mM) was the most potent cation in inhibiting radioligand binding. Calcium entry blocking drugs of different chemical classes inhibited [3H]nifedipine binding, with a rank potency order of: nifedipine much greater than D600 = verapamil greater than tiapamil greater than cinnarizine = prenylamine. The same potency order was observed for these drugs in inducing negative inotropic activity of isolated, electrically stimulated rabbit papillary muscle. The stereoselectivity of verapamil and D600 ((-) much greater than (+) isomers) in depressing papillary muscle contractions was not seen in [3H]nifedipine competition experiments. This presents an obstacle to accepting the equivalence of the [3H]nifedipine binding site with the myocardial Ca+2 channel. It is, however, possible that the myocardial Ca+2 channel may be associated with multiple sites of action for calcium entry blockers.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine; D010210:Papillary Muscles / Q000187:drug effects; D011725:Pyridines; D011817:Rabbits
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011725:Pyridines; D009543:Nifedipine