Bradykinin induces translocation of the protein kinase C isoforms alpha, epsilon, and zeta.
Bradykinin exerts a broad spectrum of cellular effects on different tissues. It is believed that these effects are predominantly mediated by the recently cloned B2 receptor. The mechanism of post-receptor signal transduction is not known in detail. Involvement of protein kinase C (PKC) was suggested and activation of the classical PKC isoforms alpha and beta was recently demonstrated. The aim of the present study was to investigate whether the B2 receptor also activates new (delta, epsilon) and atypical (zeta) PKC isoforms. To investigate this, chinese hamster ovary (CHO) cells, stably transfected with human B2 receptor, were used. In these cells the PKC isoforms alpha, delta, epsilon and zeta were detected by immunoblotting with specific antibodies. To monitor hormone-induced PKC translocation plasma membranes were prepared. Stimulation of the cells with bradykinin resulted in a rapid (30-60 s) translocation of the PKC isoforms alpha, epsilon, and zeta. Translocation of PKC delta was not detected. The effect of bradykinin was reduced by simultaneous addition of the receptor antagonist HOE 140, a bradykinin-related decapeptide. The data show that the B2 receptor in this cell model is able to activate, in addition to the classical PKC isoform alpha, the new PKC isoform epsilon and the atypical PKC isoform zeta. To test whether these effects are as well observed in a non-transfected cell, the experiments were repeated in human foreskin fibroblasts which naturally express high levels of B2 receptors. In this cell system similar results on PKC alpha, epsilon, and zeta were observed, suggesting that all three PKC isoforms are involved in signal transduction of the B2 receptor.
Tippmer
S
S
Institut für Diabetesforschung, München, Germany.
Quitterer
U
U
Kolm
V
V
Faussner
A
A
Roscher
A
A
Mosthaf
L
L
Müller-Esterl
W
W
Häring
H
H
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014162:Transfection
D065168:Bradykinin Receptor Antagonists; D007527:Isoenzymes; D018002:Receptors, Bradykinin; D011994:Recombinant Proteins; C065679:icatibant; D011493:Protein Kinase C; D001920:Bradykinin