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Ontogeny of Calcium Antagonist Binding Sites in Chick Brain and Heart
Author(s) -
Marangos P. J.,
Sperelakis †N.,
Patel J.
Publication year - 1984
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1984.tb02792.x
Subject(s) - nitrendipine , verapamil , antagonist , nifedipine , calcium , diltiazem , binding site , endocrinology , medicine , biology , ventricle , dihydropyridine , chemistry , receptor , biochemistry
The ontogeny of chick brain and heart ventricle calcium antagonist binding sites was determined, using [ 3 H]nitrendipine ([ 3 H]NDP), as the ligand. The binding of [ 3 H]NDP to adult heart and brain was kinetically very similar, with the former displaying a K D of 0.28 ± 0.02 n M and a B max of 138 ± 17 fmol/mg protein, and the latter a K D of 0.30 ± 0.02 n M and a B max of 160 ± 12 fmol/mg protein. The binding site in both brain and heart was highly specific for dihydropyridine calcium antagonists, such as nifedipine, nimodipine, and nisoldipine, since these drugs were several orders of magnitude more potent as inhibitors of [ 3 H]NDP binding than verapamil, methoxyverapamil, or diltiazem. The developmental appearance of [ 3 H]NDP binding sites in brain was rather gradual, with adult levels being attained just prior to birth. This was in contrast to the profile in heart ventricle which showed essentially adult levels at seven days gestation. The acquisition of [ 3 H]NDP binding sites in chick brain roughly paralleled the onset of neuronal maturation and functional activity. In both chick brain and heart, verapamil and methoxyverapamil were weak inhibitors of [ 3 H]NDP binding. However, the inhibition of binding in both tissues was markedly biphasic, with only 50% of the binding sites being susceptible to inhibition by each agent, suggesting that multiple calcium antagonist binding sites may exist in both tissues.