Inhibition by carbamazepine of various ion channels-mediated catecholamine secretion in cultured bovine adrenal medullary cells.
The effects of carbamazepine (CBZ) on 22Na+ influx, 45Ca2- influx, catecholamine secretion and cyclic GMP production were examined in cultured bovine adrenal medullary cells. 1) CBZ (40-120 mumol/l) inhibited 22Na+ influx evoked by carbachol in a concentration-dependent manner. CBZ inhibited carbachol-evoked 45Ca2- influx and catecholamine secretion at concentrations similar to those which suppressed 22Na+ influx. 2) CBZ (4-120 mumol/l) inhibited veratridine-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion. 3) CBZ (12 or 40-120 mumol/l) suppressed 56 mmol/l K(+)-evoked 45Ca2+ influx and catecholamine secretion, respectively. 4) Combination of CBZ with nitrendipine or omega-agatoxin-IVA produced further inhibition of 56 mmol/l K(+)-evoked 45Ca2+ influx and catecholamine secretion, compared to the effect of CBZ alone, whereas CBZ plus omega-conotoxin-GVIA did not produce any further inhibition. 5) CBZ (40 mumol/l) attenuated the production of cyclic GMP caused by muscarine. These results suggest that CBZ at therapeutic concentrations (16-48 mumol/l; 4-12 micrograms/ml) inhibits catecholamine secretion by interfering with nicotinic acetylcholine receptor-associated ion channels, voltage-dependent Na+ channels and N-type voltage-dependent Ca2+ channels, and may have an antimuscarinic effect in adrenal medullary cells.
Yoshimura
R
R
Department of Psychiatry, University of Occupational and Environmental Health, School of Medicine, Fukuoka, Japan.
Yanagihara
N
N
Terao
T
T
Minami
K
K
Abe
K
K
Izumi
F
F
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D004837:Epinephrine / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects*; D009116:Muscarine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D020867:omega-Agatoxin IVA
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D007473:Ion Channels; D011978:Receptors, Nicotinic; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D002220:Carbamazepine; D014701:Veratridine; D009116:Muscarine; D009568:Nitrendipine; D012964:Sodium; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine