Diazepam-stimulated increases in the synaptosomal uptake of 45Ca2+: reversal by dihydropyridine calcium channel antagonists.
Pharmacologically relevant concentrations of benzodiazepines have previously been reported to increase 45Ca2+ uptake into synaptosomes. This observation, coupled with the recent report that nifedipine may block the hypnotic effect of flurazepam, led us to study the effects of nifedipine and nitrendipine on 45Ca2+ uptake into synaptosomes. Diazepam (1 microM) significantly increased the uptake of 45Ca2+ to a crude synaptosomal fraction (P2) prepared from rat cerebral cortex and depolarized with 55 mM K+. Nifedipine (1 microM) did not alter the uptake of Ca2+, while nitrendipine (1 microM) reduced uptake by 37%. Both nifedipine and nitrendipine completely antagonized the ability of diazepam to increase 45Ca2+ uptake following K+ depolarization. These observations support the notion that the pharmacologic actions of benzodiazepines may be mediated through effects on a calcium channel.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology*; D004095:Dihydropyridines; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D004095:Dihydropyridines; D011725:Pyridines; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D009543:Nifedipine; D002122:Calcium Chloride; D003975:Diazepam; D002118:Calcium