Bradykinin-induced growth inhibition of normal rat kidney (NRK) cells is paralleled by a decrease in epidermal-growth-factor receptor expression.
Normal rat kidney fibroblasts, grown to density arrest in the presence of epidermal growth factor (EGF), can be induced to undergo phenotypic transformation by treatment with transforming growth factor beta or retinoic acid. Here we show that bradykinin blocks this growth-stimulus-induced loss of density-dependent growth arrest by a specific receptor-mediated mechanism. The effects of bradykinin are specific, and are not mimicked by other phosphoinositide-mobilizing agents such as prostaglandin F2 alpha. Northern-blot analysis and receptor-binding studies demonstrate that bradykinin also inhibits the retinoic acid-induced increase in EGF receptor levels in these cells. These studies provide additional evidence that EGF receptor levels modulate EGF-induced expression of the transformed phenotype in these cells.
Van Zoelen
E J
EJ
Department of Cell Biology, University of Nijmegen, Faculty of Science, The Netherlands.
Peters
P H
PH
Afink
G B
GB
Van Genesen
S
S
De Roos
D G
DG
Van Rotterdam
W
W
Theuvenet
A P
AP
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000096:biosynthesis*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats
D010716:Phosphatidylinositols; D066246:ErbB Receptors; D001920:Bradykinin