Benzodiazepine interactions at neuronal and smooth muscle Ca2+ channels

• Published in: European journal of pharmacology Vol. 134; no. 2; p. 189
• Main Authors: Rampe, D, Triggle, D J
• Format: Journal Article
• Language: English
• Published: Netherlands 10.02.1987
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Animals; Anti-Anxiety Agents - pharmacology; Benzodiazepines; Calcium Radioisotopes; Guinea Pigs; Ileum - drug effects; In Vitro Techniques; Ion Channels - drug effects; Ion Channels - metabolism; Kinetics; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Neurons - drug effects; Neurons - metabolism; Nitrendipine - metabolism; Receptors, GABA-A - drug effects
• ISSN: 0014-2999
• DOI: 10.1016/0014-2999(87)90165-8

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.