title: Benzodiazepine interactions at neuronal and smooth muscle Ca2+ channels.
abstract: 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.
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D002132:Calcium Radioisotopes; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009568:Nitrendipine / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D002132:Calcium Radioisotopes; D007473:Ion Channels; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine