Paradoxical nifedipine facilitation of Ca-45 uptake into rat hippocampal synaptosomes

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Joana Costa (Author) Other; Lobo, MG (Author) ICBAS; Paulo Correia de Sá (Author) ICBAS

Journal

Title: European Journal of Pharmacology

Vol. 544 No. 1-3

Pages: 39-48

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-000-25X

DOI: 10.1016/j.ejphar.2006.06.040

Abstract (EN): Nifedipine has a high incidence of neurologic adverse reactions as compared with other dilrydropyridine CavI (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 Ca-45 uptake by rat hippocampal synaptosomes. In the nanomolar range (0.001-0.3 mu M), nifedipine decreased Ca-45 uptake in a cadmium-sensitive manner. In contrast with nitrendipine (0.001-10 mu M), nifedipine consistently facilitated 45Ca accumulation when used in low micromolar concentrations (0.3-10 mu M). The cadmium-insensitive nifedipine facilitation became less evident upon increasing veratridine concentration from 5 to 20 mu M and was not detected when the synaptosomes where depolarised with 30 mM KCl. Na+ substitution by N-methyl-D-glucamme (132 mM) or blockade of Na+ currents with tetrodotoxin (1 mu M) both prevented nifedipine excitation. The Na+/Ca2+-exchanger inhibitor, KB-R7943 (3-50 mu M), did not reproduce nifedipine actions. Data suggest that tetrodotoxin-sensitive Na+ channels may operate paradoxical nifedipine facilitation of Ca-45 uptake by rat hippocampal synaptosomes.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10