The effects of SEA0400, a selective inhibitor of the Na(+)/Ca(2+) exchanger 
(NCX), on Na(+)-dependent Ca(2+) uptake and catecholamine (CA) release were 
examined in bovine adrenal chromaffin cells that were loaded with Na(+) by 
treatment with ouabain and veratridine. SEA0400 inhibited Na(+)-dependent 
(45)Ca(2+) uptake and CA release, with the IC(50) values of 40 and 100 nM, 
respectively. The IC(50) values of another NCX inhibitor KB-R7943 were 1.8 and 
3.7 microM, respectively. These results indicate that SEA0400 is about 40 times 
more potent than KB-R7943 in inhibiting NCX working in the reverse mode. In 
intact cells, SEA0400 and KB-R7943 inhibited CA release induced by acetylcholine 
and DMPP. The IC(50) values of SEA0400 were 5.1 and 4.5 microM and the values of 
KB-R7943 were 2.6 and 2.1 microM against the release induced by acetylcholine 
and DMPP, respectively, indicating that the potency of SEA0400 is about a half 
of that of KB-R7943 in inhibiting the nicotinic receptor-mediated CA release. 
The binding of [(3)H]nicotine with nicotinic receptors was inhibited by SEA0400 
(IC(50) = 90 microM) and KB-R7943 (IC(50) = 12 microM). From these results, it 
is concluded that unlike KB-R7943, SEA0400 has a potent and selective action on 
NCX in bovine adrenal chromaffin cells.