Effects of HOE 694--a novel inhibitor of Na+/H+ exchange--on NIH 3T3 fibroblasts expressing the RAS oncogene.
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.
Wöll
E
E
Department of Physiology, Hoechst A.G., Frankfurt, Germany.
Ritter
M
M
Offner
F
F
Lang
H J
HJ
Schölkens
B
B
Hüssinger
D
D
Lang
F
F
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*
D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine