PT - JOURNAL ARTICLE AU - Reiji Yoshimura AU - Nobuyuki Yanagihara AU - Takeshi Terao AU - Yasuhito Uezono AU - Yumiko Toyohira AU - Susumu Ueno AU - Kazuhiko Abe AU - Futoshi Izumi TI - Carbamazepine-Induced Up-regulation of Voltage-dependent Na<sup>+</sup> Channels in Bovine Adrenal Medullary Cells in Culture DP - 1998 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 441--447 VI - 287 IP - 2 4099 - http://jpet.aspetjournals.org/content/287/2/441.short 4100 - http://jpet.aspetjournals.org/content/287/2/441.full SO - J Pharmacol Exp Ther1998 Nov 01; 287 AB - Treatment of cultured bovine adrenal medullary cells with carbamazepine (CBZ) for 5 days caused an increase in catecholamine secretion induced by veratridine, an activator of voltage-dependent Na+channels. However, no increase was stimulated by carbachol, an agonist of nicotinic receptors, or by 56 mM K+, a depolarizing agent that activates voltage-dependent Ca++ channels. CBZ (30 μg/ml) treatment enhanced veratridine-induced catecholamine secretion in a time-dependent manner (increases of 25%, 65% and 70% for 3, 5 and 7 days of treatment, respectively). CBZ treatment (5 days) increased veratridine-induced catecholamine secretion in a concentration-dependent manner (increases of 27%, 36%, 45% and 55% at 10, 15, 20 and 30 μg/ml of CBZ, respectively). CBZ treatment also increased 22Na+ influx and45Ca++ influx stimulated by veratridine. The stimulatory effect of CBZ treatment on catecholamine secretion was blocked by either actinomycin D or cycloheximide, an inhibitor of protein synthesis. Additive responses of catecholamine secretion and22Na+ influx induced by veratridine were associated with combined exposure of the cells to CBZ and dibutyryl cyclic AMP. CBZ treatment (30 μg/ml, 5 days) significantly increased the specific binding of [3H]saxitoxin to cell membranes. A Scatchard analysis of [3H]saxitoxin binding revealed that CBZ increased the Bmax value without any change in the dissociation constant. These findings suggest that CBZ up-regulates the density and activity of voltage-dependent Na+ channels. The American Society for Pharmacology and Experimental Therapeutics