Carbamazepine-induced up-regulation of voltage-dependent Na+ channels in bovine adrenal medullary cells in culture.
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 microg/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 microgram/ml of CBZ, respectively). CBZ treatment also increased 22Na+ influx and 45Ca++ 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 and 22Na+ influx induced by veratridine were associated with combined exposure of the cells to CBZ and dibutyryl cyclic AMP. CBZ treatment (30 microg/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.
Yoshimura
R
R
Department of Psychiatry, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Yanagihara
N
N
Terao
T
T
Uezono
Y
Y
Toyohira
Y
Y
Ueno
S
S
Abe
K
K
Izumi
F
F
D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015640:Ion Channel Gating; D017136:Ion Transport; D007546:Isoquinolines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D062687:Sodium Channel Agonists; D013449:Sulfonamides; D015854:Up-Regulation / Q000187:drug effects*; D014701:Veratridine / Q000494:pharmacology
D000927:Anticonvulsants; D002395:Catecholamines; D007546:Isoquinolines; D062687:Sodium Channel Agonists; D013449:Sulfonamides; D003609:Dactinomycin; D002220:Carbamazepine; D003994:Bucladesine; D014701:Veratridine; D002217:Carbachol; D003513:Cycloheximide; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D011188:Potassium