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.