125I-iodipine, a new high affinity ligand for the putative calcium channel

The compound 1,4-dihydro-2,6-dimethyl-4-(2-trifluoromethylphenyl)-3, 5-pyridinecarboxylic acid 2-(amino-ethyl)ethylester was reacted with N-succinimidyl 3-(4-hydroxy, 5-125I-iodophenyl)propionate (2,200 Ci/mmol. The purified, 125I-labelled product of this reaction is termed 125I-iodipine and has a specific activity of approximately 2,200 Ci/mmol on the date of preparation. 125I-Iodipine binds reversibly in a saturable manner and with high affinity to skeletal muscle and brain membranes with KD values at 25 degrees C of 400 and 60 pmol/l, respectively. The binding of 125I-iodipine is stereoselectively inhibited by chiral 1,4-dihydropyridine calcium channel blockers. 125I-Iodipine labelled sites also recognize the recently described 1,4-dihydropyridine calcium channel activators and discriminate the chemically unrelated compounds (-)- and (+)verapamil, (-)- and (+)methoxyverapamil and d- and l-cis diltiazem. It is concluded that 125I-iodipine labels the putative calcium channel.