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.
D000818:Animals; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D011869:Radioligand Assay; D013696:Temperature; D013997:Time Factors
D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D007473:Ion Channels; C041028:iodipine