Abstract
The binding properties of the 1,4-dihydropyridine calcium channel antagonist, [3H](+)PN 200-110, were studied in rat cerebral cortical and cardiac homogenates (37°C, Krebs phosphate buffer). Specific binding of [3H](+)PN 200-110 was saturable, reversible, and of high affinity (Kd values are 35 and 64 pM for the cerebral cortex and heart, respectively). In parallel studies with [3H](+)PN 200-110, the dissociation constant of [3H]nitrendipine was 10-12 times higher. Substituted dihydropyridine calcium channel antagonists and agonists competitively inhibited specific [3H](+)PN 200-110 binding, but d-cis diltiazem enhanced and verapamil incompletely inhibited [3H](+)PN 200-110 binding in both the cerebral cortex and the heart. The effects of diltiazem and verapamil on [3H](+)PN 200-110 binding were due mainly to alterations in the dissociation constant (Kd), without alterations in the binding density (Bmax). The new [3H](+)PN 200-110 receptor binding assay is remarkable for its low degree of nonspecific binding as compared to [3H]nitrendipine at physiological temperatures. [3H(+)PN 200-110 is a useful ligand for the further analysis of the dihydropyridine binding sites associated with calcium channels.
Original language | English (US) |
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Pages (from-to) | 721-732 |
Number of pages | 12 |
Journal | Life Sciences |
Volume | 35 |
Issue number | 7 |
DOIs | |
State | Published - Aug 13 1984 |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- Pharmacology, Toxicology and Pharmaceutics(all)