title: Inhibition of normal human granulopoiesis in vitro by amiloride: evidence for the involvement of facilitated sodium influx in the induction of differentiation.
abstract: The formation of colonies by normal human bone marrow granulopoietic progenitor cells in vitro in soft agar was inhibited in a simple, dose-dependent manner by amiloride (50% inhibitory concentration 26.4 +/- 3.4 microM, n = 9). Such inhibition was reversible and is evidence for the involvement of amiloride-sensitive sodium influx in granulopoietic cell proliferation. Colony-forming cells were capable of some proliferation at concentrations of amiloride 3-fold in excess of that required to inhibit full colony formation. A two-stage model is invoked to explain this observation: an early amiloride-insensitive stage and a late amiloride-sensitive stage which includes terminal differentiation. We conclude that the cellular mechanism by which differentiation is induced includes activation of the amiloride-sensitive sodium influx channel, which would indicate a new approach to the therapeutic induction of differentiation in vivo.
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D010042:Ouabain; D000584:Amiloride; D012964:Sodium