SELECTIVE-INHIBITION BY RILUZOLE OF VOLTAGE-DEPENDENT SODIUM-CHANNELSAND CATECHOLAMINE SECRETION IN ADRENAL CHROMAFFIN CELLS

Citation
H. Yokoo et al., SELECTIVE-INHIBITION BY RILUZOLE OF VOLTAGE-DEPENDENT SODIUM-CHANNELSAND CATECHOLAMINE SECRETION IN ADRENAL CHROMAFFIN CELLS, Naunyn-Schmiedeberg's archives of pharmacology, 357(5), 1998, pp. 526-531
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
0028-1298
Volume
357
Issue
5
Year of publication
1998
Pages
526 - 531
Database
ISI
SICI code
0028-1298(1998)357:5<526:SBROVS>2.0.ZU;2-E
Abstract
The examined the effects of riluzole, a neuroprotective drug, on volta ge-dependent Na channels, nicotinic receptors, and voltage-dependent C a channels, as well as catecholamine secretion, in comparison with tho se of verapamil and nicardipine, in primary cultures of bovine adrenal chromaffin cells. Riluzole inhibited veratridine-induced Na-22 influx via voltage-dependent Na channels even in the presence of ouabain. an inhibitor of Na,K-ATPase. Blockade of Na channels by riluzole was con centration-dependent with an IC50 of 5.3 mu M. It was associated with a similar concentration-related reduction of veratridine-induced Ca-45 influx via voltage-dependent Ca channels, and of catecholamine secret ion. Riluzole had no effect on Ca-45 influx caused by high K, which di rectly activates voltage-dependent Ca channels, and on nicotine-induce d Na-22 influx, which passes through the nicotinic receptors. Verapami l and nicardipine attenuated Na-22 influx caused by veratridine or nic otine at the same concentrations as they suppressed high K-induced Ca- 45 influx. The inhibitory effect of riluzole on veratridine-induced Na -22 influx disappeared at high concentrations of veratridine. A potent iation of veratridine (site 2 toxin)-induced Na-22 influx caused by al pha-scorpion venom (site 3 toxin), beta-scorpion venom (site 4 toxin), or brevetoxin PbTx-3 (site 5 toxin), occurred in the presence of rilu zole in the same manner as in control cells. These results suggest tha t riluzole binds to the veratridine site in voltage-dependent Na chann els. It does not impair the cooperative interaction between the functi onal peptide segments of Na channels, but selectively inhibits gating of Na channels, thereby reducing Ca influx via Ca channels and catecho lamine secretion. In contrast, verapamil and nicardipine suppress Na i nflux both Na channels and nicotinic receptors.