The binding of [3H]nitrendipine to receptors for calcium channel antagonists in the heart, cerebral cortex, and ileum of rats

• Published in: Life sciences (1973) Vol. 30; no. 25; p. 2191
• Main Authors: Ehlert, F J, Roeske, W R, Itoga, E, Yamamura, H I
• Format: Journal Article
• Language: English
• Published: Netherlands 21.06.1982
• Subjects: Animals; Binding Sites - drug effects; Calcium Channel Blockers - metabolism; Calcium Channel Blockers - pharmacology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Heart - drug effects; Ileum - drug effects; Ileum - metabolism; In Vitro Techniques; Kinetics; Male; Muscle, Smooth - metabolism; Myocardium - metabolism; Nifedipine - analogs & derivatives; Nifedipine - metabolism; Nifedipine - pharmacology; Nitrendipine; Pyridines - metabolism; Rats; Rats, Inbred Strains; Verapamil - metabolism; Verapamil - pharmacology
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(82)90293-4

The binding properties of the calcium channel antagonist, [3H]nitrendipine, were investigated in homogenates of the rat cerebral cortex, heart and ileum. The specific component of [3H]nitrendipine binding was consistent with mass-action behavior and was characterized by a high affinity dissociation constant in the range of 0.1-0.3 nM. A variety of other calcium channel antagonists inhibited the binding of [3H]nitrendipine with Ki's that agree generally with the ability of these drugs to block contractions of cardiac and smooth muscle. The inhibition of [3H]nitrendipine binding by other dihydropyridines was consistent with competitive antagonism whereas the inhibition caused by verapamil and D600 resembled negative heterotropic cooperativity. Consistent with this latter postulate was the observation that the kinetics of [3H]nitrendipine binding are altered by verapamil, with both the association rate and the dissociation rate being increased. La+3 and several divalent cations caused an inhibition of [3H]nitrendipine with the rank order of potency being Cd+2 greater than La+3 greater than Ni+2 greater than Co+2 = Mn+2 greater than Mg+2 = Ba+2 greater than Ca+2.