Benzodiazepine interactions at neuronal and smooth muscle Ca²⁺ channels

Ro 5-4864 and PK 11195, ligands for the peripheral benzodiazepine binding site, blocked ⁴⁵Ca²⁺ uptake into depolarized guinea-pig cortical synaptosomes. The fast phase of uptake was significantly more sensitive than the slow phase. The central benzodiazepine ligands, Ro 15-1788 and β-CCE at 10^-4 and 5 × 10^-5 M respectively, were less effective and did not discriminate between fast and slow uptake phases. Ro 5-4864 and PK 11195 inhibited and potentiated respectively the binding of [³H]nitrendipine to synaptosomes by effects on the K_D value. PK 11195 (10^-5 M), blocked K⁺ depolarization and Bay K 8644-induced tension responses in guinea-pig ileal longitudinal smooth muscle. Benzodiazepines do interact with voltage-dependent Ca²⁺ channels but the present data are insufficient to prove direct coupling of peripheral benzodiazepine sites with Ca²⁺ channels.