Calcium channel activation: a different type of drug action

Depolarization of NG108-15 (neuroblastoma-glioma) cells causes an increase in 45Ca2+ influx. This effect is blocked by low concentrations of dihydropyridines such as nitrendipine and by other blockers of voltage-sensitive calcium channels such as D-600, diltiazem, and Cd2+. Two other dihydropyridines, BAY K8644 and CGP 28392, have the opposite effect. Low concentrations of these compounds enhance depolarization-induced 45Ca2+ influxes. BAY K8644 is more effective than CGP 28392. Both agents have no effect on fluxes measured under nondepolarizing conditions. The effects of BAY K8644 and CGP 28392 can be inhibited by nitrendipine, D-600, diltiazem, or Cd2+. Whereas the interaction between nitrendipine and BAY K8644 is shown to be competitive in nature, that between BAY K8644 and D-600 is shown to be noncompetitive. These results indicate that dihydropyridines show a variety of effects on calcium channels, ranging from agonistic through partially agonistic to antagonistic. Moreover, the results also indicate that dihydropyridines and D-600 exert their effects on calcium channels at different sites.