Dihydropyridine calcium channel antagonist binding in non-mammalian vertebrates: characterization and relationship to 'peripheral-type' binding sites for benzodiazepines

The densities of dihydropyridine calcium antagonist binding sites were examined in brains and cardiac tissues of representative species from 4 classes of non-mammalian vertebrates (avies, pigeon; amphibia, frog; reptilia; chameleon; and osteichytes, trout) previously shown to have low or undetectable levels of 'peripheral-type' binding sites for benzodiazepines. Dihydropyridine binding sites were present in brain and cardiac tissue of these 4 classes of non-mammalian vertebrates. The apparent dissociation constants for [³H]nitrendipine in non-mammalian vertebrates were comparable to those found in mammalian (rat) tissues. The densities of [³H]nitrendipine binding sites in brain and cardiac tissues were highest in the pigeon, with lower densities in tissues from chameleon, frog and trout. The densities of dihydropyridine binding sites in the latter tissues were comparable to those observed in the rat. Thus, dihydropyridine binding sites are phylogenetically diverse yet have similar kinetic characteristics in mammals and non-mammalian vertebrates. Despite the pharmacologic evidence that links dihydropyridine binding sites and peripheral binding sites for benzodiazepines in mammals, the earlier evolutionary appearance of the former sites suggest that even though they may share one or more common effector mechanisms, they are discrete entities.