Release of norepinephrine and dopamine from brain vesicular preparations: Effects of calcium antagonists

1. The calcium antagonists D-600 (1-10 μM) and diltiazem (10-25 μM) inhibit K⁺-evoked release of [³H]norepinephrine from guinea pig cerebral cortical vesicular preparations. The inhibition of release is partially reversed by increasing concentrations of calcium to 2 m M. Diltiazem at 100 μM has no effect on K⁺-evoked release of [³H]norepinephrine at 0.15 m M calcium but does inhibit release at 2.0 m M calcium. 2. The calcium antagonist nifedipine and dantrolene, an agent purported to antagonize release of calcium from intracellular storage sites, have no effect on K⁺-evoked release of [³H]norepinephrine. 3. The calcium antagonists D-600 (1 μM) and diltiazem (10 μM) inhibit K⁺-evoked release of [³H]dopamine from guinea pig striatal vesicular preparations. Higher concentrations of drug, namely, 10 μM for D-600 and 100 μM for diltiazem, cause a potentiation rather than an inhibition of K⁺-evoked release. The potentiation is reduced in magnitude upon raising the extracellular calcium to 2.0 m M. Indeed, 10 μM D-600 then inhibits K⁺-evoked release of [³H]dopamine. 4. The results indicate that putative calcium antagonists can have both inhibitory and facilitory effects on calcium-dependent K⁺-evoked release of catecholamines from central synaptic endings. Furthermore, certain peripheral calcium antagonists such as nifedipine and dantrolene may prove ineffective in central systems.