Binding of a calcium antagonist, [3H]nitrendipine, to high affinity sites in bovine aortic smooth muscle and canine cardiac membranes
| Autor: | Lewis T. Williams, Patrice Tremble |
|---|---|
| Rok vydání: | 1982 |
| Předmět: |
Vascular smooth muscle
Nifedipine Stereochemistry Pyridines Heart Ventricles Nisoldipine chemistry.chemical_element Calcium Binding Competitive Ion Channels Muscle Smooth Vascular Dogs Nitrendipine medicine Animals Binding site Rapid Publications Aorta Binding Sites Membranes Calcium channel General Medicine Calcium Channel Blockers Dissociation constant chemistry Cattle medicine.drug |
| Zdroj: | The Journal of clinical investigation. 70(1) |
| ISSN: | 0021-9738 |
| Popis: | [(3)H]Nitrendipine, a potent calcium channel antagonist [3-ethyl-5-methyl-1-1,4-dihydro-2,6 - dimethyl - 4 - (3 - nitrophenyl) - 3,5 - pyridine carboxylate], was used to label high affinity binding sites on membranes prepared from bovine aortic smooth muscle. The binding of [(3)H]nitrendipine is rapid (t(1/2) < 5 min) and reversible at 37 degrees C. The binding sites have a high affinity for [(3)H]nitrendipine with an equilibrium dissociation constant of 2.1 nM. The density of sites is 40-60 fmol/mg of membrane protein. Analogues of nitrendipine compete for the binding sites with affinities consistent with their known biological effects as calcium antagonists. Nisoldipine, [isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine carboxylate], a calcium antagonist more potent than nifedipine [2,6-dimethyl-3,5-dicarbomethoxy-4-(2-nitrophenyl)-1,4-dihydropyridine] in relaxing vascular smooth muscle, has an affinity three-fold higher than that of nifedipine in competing for the binding sites. A biologically inactive derivative of nifedipine does not compete for [(3)H]nitrendipine binding. Verapamil (alpha-isopropyl-alpha[(N-methyl - N-homoveratryl) -alpha-aminopropyl]-3,4-dimethyoxyphenyl acetonitrile), a structurally different calcium antagonist, only partially (25%) inhibits binding at high concentrations (1 muM). Prazosin, an alpha adrenergic antagonist does not compete for [(3)H]nitrendipine binding sites. The binding of [(3)H]nitrendipine is not affected by 1.5 mM calcium. Canine cardiac membranes also have high affinity [(3)H]nitrendipine binding sites, (K(D) = 6 nM) but bovine erythrocytes do not. The relative affinities of nisoldipine and nifedipine for the cardiac membrane binding sites reflect the relative activities of these compounds as calcium channel antagonists. These results suggest that the [(3)H]nitrendipine binding sites are the sites through which dihydropyridines act as calcium channel antagonists. |
| Databáze: | OpenAIRE |
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