A New Ca-Antagonist, CD-349, Binding to the Ca-Channel of Rat Myocardium and Brain and Hog Coronary Artery

抄録

The binding to a Ca-channel of a novel 1, 4-dihydropyridine (DHP) Ca-antagonist, 2-nitratopropyl 3-nitratopropyl 2, 6-dimethyl-4-(3-nitrophenyl)-1, 4-dihydropyridine-3, 5-dicarboxylate (CD-349), was studied in rat myocardium and brain and hog coronary artery, and the binding was compared with that of other DHPs. In rat myocardium, the binding reaction of [³H]CD-349 was faster than that of nitrendipine (NTD). The association rate constant of [³H]CD-349 was about 10 times higher than that of [³H] NTD. The dissociation rate was also higher than that of [³H]NTD. Scatchard plot analysis of [³H]CD-349 binding showed one high affinity site for CD-349. The dissociation constant (K_d) and maximum number of binding sites (B_max) were 333 pM and 286 fmoles/mg protein. They were almost the same as those for [³H]NTD. [³H]CD-349 and [³H]NTD bindings were dose dependently inhibited by 1, 4-DHPs: nifedipine, nimodipine, nicardipine and CD-349. The order of the inhibitory potency of these drugs was CD-349>nicardipine>nimodipine>nifedipine, when [³H]CD-349 and [³H]NTD were used as the ligands. Similar results were obtained for rat brain and hog coronary artery. [³H]-CD-349 binding was not changed by α- or β-adrenergic, cholinergic, histaminergic or serotonergic agents in rat myocardium. From these results, it is suggested that CD-349 binds to the Ca-channel reversibly with high affinity due to its high association rate for the site.