Inhibition of endothelin-mediated topoisomerase I activation by pertussis toxin.
Cultured rat mesangial cells contain high affinity endothelin (ET) receptors at high densities. Exposure of these cells to ET resulted in a transient activation of topoisomerase I extractable activity, which reached its maximum value at approximately 2 min and returned to basal value after approximately 10 min of treatment. The activation of this enzyme was dependent upon the concentration of ET added. Incubation of the cells with pertussis toxin inhibited ET-induced increases in topoisomerase I activity in a concentration-dependent manner, suggesting that involvement of pertussis toxin-sensitive GTP-binding protein in ET-mediated action. Endothelin had no detectable effect upon extractable topoisomerase II activity.
Nambi
P
P
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Wu
H L
HL
Woessner
R D
RD
Mattern
M R
MR
D000818:Animals; D002478:Cells, Cultured; D004264:DNA Topoisomerases, Type I / Q000302:isolation & purification / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology*; D004789:Enzyme Activation; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology*; D007672:Kidney Cortex / Q000201:enzymology*; D007700:Kinetics; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000502:physiology; D017466:Receptors, Endothelin; D059004:Topoisomerase I Inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D016232:Endothelins; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D059004:Topoisomerase I Inhibitors; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D004264:DNA Topoisomerases, Type I