title: N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) stimulation of K+ transport in a human salivary epithelial cell line.
abstract: Treatment of a human salivary epithelial cell line, HSG-PA, with the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7; 20-70 microM) increased 86Rb (K+) influx and efflux in a manner similar to that resulting from muscarinic (carbachol; Cch) or calcium ionophore (A23187) stimulation. Unlike the Cch or A23187 responses, the W7 responses were not blocked by 0.1 mM atropine (muscarinic antagonist) or phorbol-12-myristate-13-acetate (0.1 microM). Like Cch- or A23187-stimulated 86Rb fluxes, W7-stimulated 86Rb fluxes were substantially blocked by the K+ channel inhibitors quinine (0.25 mM) and scorpion venom-containing charybdotoxin (33 micrograms/mL), while 5 mM tetraethylammonium chloride (K+ channel blocker), furosemide (0.1 mM; Na+,K+,2Cl- co-transport inhibitor) and ouabain (10 microM; Na+,K(+)-ATPase inhibitor) were ineffective. Purified charybdotoxin (10 nM) also blocked W7-stimulated 86Rb influx, as well as 86Rb influx stimulated by Cch or A23187. Although Quin 2 fluorescence measurements indicated that W7 increased free intracellular Ca2+ concentration ([Ca2+]i), the magnitude of the increase appeared to be insufficient to solely account for the W7-stimulated increases in 86Rb fluxes (i.e. K+ channel activity). Ca2+ was involved in the W7 response, however, as lack of Ca2+ in the incubation medium reduced the W7-stimulated increases in 86Rb influx and efflux. Taken together, our results suggest that W7 increased K+ fluxes in HSG-PA cells by interacting, directly or indirectly, with the K+ transport machinery (K+ channels) in a manner different from that observed during muscarinic stimulation, and also in a manner not accounted for solely by the formation of a typical muscarinic- or calcium ionophore-generated calcium signal.
authors.affiliation: Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
authors.forename: L
authors.initials: L
authors.lastname: Patton
authors.forename: J
authors.initials: J
authors.lastname: Ship
authors.forename: R
authors.initials: R
authors.lastname: Wellner
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002460:Cell Line / Q000187:drug effects; D018999:Charybdotoxin; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D012414:Rubidium Radioisotopes; D012469:Salivary Glands / Q000187:drug effects* / Q000378:metabolism; D012604:Scorpion Venoms / Q000494:pharmacology; D013449:Sulfonamides / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000634:Aminoquinolines; D002147:Calmodulin; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D012604:Scorpion Venoms; D013449:Sulfonamides; D018999:Charybdotoxin; C017967:W 7; C035739:Quin2; D002118:Calcium