title: High-affinity and selectivity of neosurugatoxin for the inhibition of 22Na influx via nicotinic receptor-ion channel in cultured bovine adrenal medullary cells: comparative study with histrionicotoxin.
abstract: In cultured bovine adrenal medullary cells, neosurugatoxin and histrionicotoxin inhibited carbachol-induced influx of 22Na, 45Ca and secretion of catecholamines with IC50 of 27 nM and 3 microM, respectively. The inhibitory effects of neosurugatoxin were reversed by the increased concentrations of carbachol, whereas those of histrionicotoxin were not. Histrionicotoxin at concentrations higher than 10 microM also reduced veratridine-induced influx of 22Na, 45Ca and secretion of catecholamines, while neosurugatoxin had no effects. High K-induced 45Ca influx and catecholamine secretion were not altered by either neosurugatoxin or histrionicotoxin. The present findings suggest (1) neosurugatoxin competitively inhibits nicotinic receptor-ion channel complex at nanomolar concentrations, but has no effects on voltage-dependent Na channel and voltage-dependent Ca channel; (2) histrionicotoxin at micromolar concentrations non-competitively suppresses nicotinic receptor-ion channel complex. Higher concentrations of histrionicotoxin also interferes with voltage-dependent Na channel, but has no effect on voltage-dependent Ca channel; (3) neosurugatoxin, due to its high-affinity and selectivity, may be a useful probe for studying nicotinic receptors in nervous tissues.
authors.affiliation: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Wada
authors.forename: Y
authors.initials: Y
authors.lastname: Uezono
authors.forename: M
authors.initials: M
authors.lastname: Arita
authors.forename: K
authors.initials: K
authors.lastname: Tsuji
authors.forename: N
authors.initials: N
authors.lastname: Yanagihara
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: F
authors.initials: F
authors.lastname: Izumi
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000664:Amphibian Venoms / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D008978:Mollusk Venoms / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000378:metabolism* / Q000502:physiology; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: D000664:Amphibian Venoms; D008978:Mollusk Venoms; D011978:Receptors, Nicotinic; C036793:neosurugatoxin; D002217:Carbachol; D012964:Sodium; C007948:histrionicotoxin; D014403:Tubocurarine