High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers.
Antibodies with high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers have been produced in rabbits by immunization with dihydropyridine-protein conjugates. Anti-dihydropyridine antibodies were found to specifically bind [3H]nitrendipine, [3H]-nimodipine, [3H]nisoldipine, and [3H]PN 200-110 (all 1,4-dihydropyridine Ca2+-channel blockers) with high affinity, while [3H]verapamil, [3H]diltiazem, and [3H]trifluoperazine were not recognized. The average dissociation constant of the [3H]nitrendipine-antibody complex was 0.06 (+/- 0.02) X 10(-9) M for an antiserum studied in detail and ranged from 0.01 to 0.24 X 10(-9) M for all antisera. Inhibition of [3H]nitrendipine binding was specific for the 1,4-dihydropyridine Ca2+-channel modifiers and the concentrations required for half-maximal inhibition ranged between 0.25 and 0.90 nM. Structurally unrelated Ca2+-channel blockers, calmodulin antagonists, inactive metabolites of nitrendipine, and UV-inactivated nisoldipine did not modify [3H]nitrendipine binding to the anti-dihydropyridine antibodies. Dihydropyridines without a bulky substituent in the 4-position of the heterocycle were able to displace [3H]nitrendipine binding, but the concentrations required for half-maximal inhibition were greater than 800 nM. In summary, anti-dihydropyridine antibodies have been shown to have high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers and to exhibit dihydropyridine binding properties similar to the membrane receptor for the 1,4-dihydropyridine Ca2+-channel blockers.
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D002121:Calcium Channel Blockers / Q000276:immunology*; D015220:Calcium Channels; D004095:Dihydropyridines; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009568:Nitrendipine; D011725:Pyridines / Q000276:immunology*; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000276:immunology; D013329:Structure-Activity Relationship; D014316:Tritium
D000906:Antibodies; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D011725:Pyridines; D011978:Receptors, Nicotinic; D014316:Tritium; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D009543:Nifedipine