Colony-stimulating factor 1-induced Na+ influx into human monocytes involves activation of a pertussis toxin-sensitive GTP-binding protein.
Colony-stimulating factor 1 (CSF-1) regulates the survival, growth, and differentiation of monocytes through binding to a single class of high affinity receptors. The present studies demonstrate that the interaction of CSF-1 with monocyte membranes is associated with a 2.4-fold increase in specific binding of the GTP analogue, GTP gamma S. Scatchard analysis of the GTP gamma S binding data indicated that CSF-1 stimulates GTP binding by increasing the affinity, rather than the number, of available sites. This stimulation of GTP binding by CSF-1 was also associated with an increase in GTPase activity. Furthermore, the CSF-1-induced stimulation of GTPase activity was sensitive to pertussis toxin. We also demonstrate that CSF-1 stimulates Na+ influx into monocytes by an amiloride-sensitive mechanism, presumably the Na+/H+ antiport. This CSF-1-stimulated influx of Na+ was further associated with an increase in Na+,K+-ATPase activity. Moreover, this stimulation of Na+ influx and Na+,K+-ATPase activity by CSF-1 was sensitive to pertussis toxin. Finally, we demonstrate that CSF-1-induced proliferation is also a pertussis toxin-sensitive event. The present findings thus suggest: 1) that the CSF-1 receptor is linked to a pertussis toxin-sensitive G protein; and 2) that a pertussis toxin-sensitive G protein is involved in the induction of Na+ influx by CSF-1.
Imamura
K
K
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Kufe
D
D
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D020558:GTP Phosphohydrolases / Q000097:blood; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D012964:Sodium / Q000097:blood*; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood; D013873:Thionucleotides / Q000097:blood; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D012964:Sodium; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase