Neomycin inhibits PDGF-induced IP3 formation and DNA synthesis but not PDGF-stimulated uptake of inorganic phosphate in C3H/10T1/2 fibroblasts.
Porcine PDGF was found to increase [3H]inositol trisphosphate, [3H]thymidine incorporation and 32P-labelling of polyphosphoinositides in C3H/10T1/2 Cl 8 fibroblasts. These responses to PDGF stimulation were all inhibited by 5 mM neomycin, a polycationic aminoglycoside formerly known to inhibit polyphosphoinositide turnover. PDGF also markedly increased the cellular uptake of inorganic [32P]Pi. This response of PDGF was not inhibited by neomycin (5 mM). Thus, neomycin inhibited PDGF-induced IP3 formation, 32P-labelling of polyphosphoinositides and DNA synthesis, but not cellular uptake of inorganic phosphate. These effects of neomycin suggest a bifurcation of the initial part of the PDGF-induced signal transduction, separating at the receptor level or before phospholipase C activation.
Vassbotn
F S
FS
Department of Biochemistry, University of Bergen, Norway.
Langeland
N
N
Holmsen
H
H
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009355:Neomycin / Q000008:administration & dosage / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D010710:Phosphates; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D015544:Inositol 1,4,5-Trisphosphate; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D009355:Neomycin; D013936:Thymidine