The actions of diazepam and diphenylhydantoin on fast and slow Ca2+ uptake processes in guinea pig cerebral cortex synaptosomes.
The activities of diazepam and diphenylhydantoin as inhibitors of the fast and slow phases of 45Ca2+ uptake in response to K+ depolarization and of [3H]nitrendipine binding were examined in guinea pig cerebral cortex synaptosomes. The slow phase of 45Ca2+ uptake was abolished in Na+-free media (choline substitution) and was more sensitive to inhibition by 3,4-dichlorobenzamil and represents a Na+-dependent Ca2+ uptake process. The fast component of uptake represents activation of voltage-dependent Ca2+ channels. Diazepam (to 300 microM) was selectively active against the fast component of 45Ca2+ uptake. The benzodiazepines Ro 11-3624 and Ro 11-3128 were similarly selective with a modest stereoselectivity against the fast component of 45Ca2+ uptake. Diphenylhydantoin (100 and 200 microM) blocked nonselectively both fast and slow phases of Ca2+ uptake. Diazepam (60 microM) and diphenylhydantoin (200 microM) blocked [3H]nitrendipine binding in a competitive manner. Diazepam and diphenylhydantoin probably exert at least part of their anticonvulsant activity by inhibition of voltage-dependent Ca2+ channels.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009568:Nitrendipine / Q000378:metabolism; D010672:Phenytoin / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002132:Calcium Radioisotopes; D010672:Phenytoin; D009568:Nitrendipine; D003975:Diazepam; D011188:Potassium; D002118:Calcium