title: Effects of HOE 694--a novel inhibitor of Na+/H+ exchange--on NIH 3T3 fibroblasts expressing the RAS oncogene.
abstract: Among the sequelae of ras oncogene expression are intracellular alkalinization and increase of cell volume, both phenomena attributed at least in part to activation of the Na+/H+ exchanger. The present study was performed to elucidate the effects of HOE 694--a novel inhibitor of the Na+/H+ exchanger--on intracellular pH, cell volume, cytoarchitecture and cell proliferation of ras oncogene expressing NIH 3T3 fibroblasts. Following transient exposure of the cells to 20 mmol/l NH3/NH4+, intracellular pH decreases sharply. The following slow realkalinization is completely blocked by 10 mumol/1 HOE 694. Half-maximal inhibition is achieved by 100 nmol/l HOE 694. Cell proliferation is inhibited by HOE 694 with similar potency, whereas the increase in cell volume and cytoskeletal transformation are not prevented, even by 10 mumol/l HOE 694.
authors.affiliation: Department of Physiology, Hoechst A.G., Frankfurt, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Wöll
authors.forename: M
authors.initials: M
authors.lastname: Ritter
authors.forename: F
authors.initials: F
authors.lastname: Offner
authors.forename: H J
authors.initials: HJ
authors.lastname: Lang
authors.forename: B
authors.initials: B
authors.lastname: Schölkens
authors.forename: D
authors.initials: D
authors.lastname: Hüssinger
authors.forename: F
authors.initials: F
authors.lastname: Lang
mesh_terms: D016475:3T3 Cells / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D015870:Gene Expression; D011905:Genes, ras; D006146:Guanidines / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine