Paradoxical nifedipine facilitation of 45Ca uptake into rat hippocampal synaptosomes.
Nifedipine has a high incidence of neurologic adverse reactions as compared with other dihydropyridine Cav1 (L-type) channel blockers used for treating cardiovascular diseases. The mechanism mediating neuronal excitation by nifedipine is still in debate. Nifedipine caused a dual role on veratridine-induced 45Ca uptake by rat hippocampal synaptosomes. In the nanomolar range (0.001-0.3 microM), nifedipine decreased 45Ca uptake in a cadmium-sensitive manner. In contrast with nitrendipine (0.001-10 microM), nifedipine consistently facilitated 45Ca accumulation when used in low micromolar concentrations (0.3-10 microM). The cadmium-insensitive nifedipine facilitation became less evident upon increasing veratridine concentration from 5 to 20 microM and was not detected when the synaptosomes where depolarised with 30 mM KCl. Na+ substitution by N-methyl-D-glucamine (132 mM) or blockade of Na+ currents with tetrodotoxin (1 microM) both prevented nifedipine excitation. The Na+/Ca2+-exchanger inhibitor, KB-R7943 (3-50 microM), did not reproduce nifedipine actions. Data suggest that tetrodotoxin-sensitive Na+ channels may operate paradoxical nifedipine facilitation of 45Ca uptake by rat hippocampal synaptosomes.
Costa
Joana
J
Laboratório de Farmacologia/UMIB, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, L. Prof. Abel Salazar, 2, 4099-003 Porto, Portugal.
Lobo
M Graça
MG
Correia-de-Sá
Paulo
P
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes / Q000493:pharmacokinetics; D002490:Central Nervous System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D009568:Nitrendipine / Q000494:pharmacology*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D013779:Tetrodotoxin; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium