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 beta-CCE at 10(-4) and 5 X 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 KD 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.