title: Inhibition by SEA0400, a selective inhibitor of Na+/Ca2+ exchanger, of Na+ -dependent Ca2+ uptake and catecholamine release in bovine adrenal chromaffin cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, The Nippon Dental University School of Life Dentistry at Niigata, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Soma
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Kuwashima
authors.forename: Chiaki
authors.initials: C
authors.lastname: Matsumura
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010647:Phenyl Ethers / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects; D012964:Sodium / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000814:Aniline Compounds; D002395:Catecholamines; D018722:Nicotinic Agonists; D010647:Phenyl Ethers; D011978:Receptors, Nicotinic; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D004246:Dimethylphenylpiperazinium Iodide; D011189:Potassium Chloride; D012964:Sodium; D013890:Thiourea; D000109:Acetylcholine; D002118:Calcium