Bradykinin-induced inhibition of cell proliferation and tyrosine kinase activity in rat mesangial cells.
The relationship between cell proliferation, protein tyrosine phosphorylation, phosphotyrosine kinase activity and bradykinin receptor activation in rat mesangial cells was investigated. We demonstrated that bradykinin (BK), through the B2 receptor, induced a dose-dependent inhibition of mesangial cell proliferation stimulated by fetal calf serum. We next found that BK induced a dose-dependent inhibition of phospho-tyrosine kinase activity. Treatments with pertussis-toxin, inhibition of phospholipase C and protein kinase C inhibitors and chelation of free cytosolic calcium did not change the bradykinin-induced inhibition of phosphotyrosine kinase. Western blot analysis of phosphotyrosinated proteins demonstrated that BK reduced tyrosine phosphorylation of several proteins among which we identified the 125-focal adhesion kinase. Taken together, these data suggest for the first time that, in proliferating rat mesangial cells, B2 receptor stimulation is able to induce, via a pertussis insensitive pathway, the inhibition of tyrosine kinase activity and mesangial cell proliferation.
Alric
C
C
Institut National de la Sante et de la Recherche Medicale, INSERM U388, Institut Louis Bugnard, CHU Rangueil, 31052 Toulouse, France.
Pecher
C
C
Schanstra
J P
JP
Bascands
J L
JL
Girolami
J P
JP
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005920:Glomerular Mesangium; D007328:Insulin / Q000494:pharmacology; D037342:Pertussis Toxin; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D065168:Bradykinin Receptor Antagonists; D004963:Estrenes; D007328:Insulin; D011760:Pyrrolidinones; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D010740:Phospholipases; D001920:Bradykinin; D002118:Calcium