Activation of human endometrial phospholipase D by bradykinin.
Bradykinin may act as a promoter of endometrial regeneration. In [3H]myristate-labelled endometrial stromal cells, bradykinin and tetradecanoylphorbol acetate (TPA) mediated activation of phospholipase D (PLD) as measured by the accumulation of [3H]phosphatidylbutanol ([3H]PtdBut). Kinetics of bradykinin-evoked PLD activation was rapid and transient, whereas the TPA response was relatively slow in onset. Bradykinin induced a dose-dependent (EC50 0.11 nM) [3H]PtdBut accumulation at concentrations at which it stimulated DNA synthesis. In [3H]inositol-labelled cells, bradykinin evoked a rapid increase in inositol phosphates which preceded the increase in [3H]PtdBut formation. Chronic pretreatment with 400 nM TPA abolished PLD activation to subsequent treatment with either TPA and bradykinin. Staurosporine, an inhibitor of protein kinase C, strongly inhibited (IC50 96 nM) TPA-induced [3H]PtdBut formation, but bradykinin-stimulated [3H]PtdBut accumulation was only partially inhibited (IC50 65 microM). The effect of bradykinin and TPA on PLD activity was synergistic, suggesting that the two agents may act via different mechanisms. These results suggest PKC-dependent and independent pathways are involved in bradykinin-induced PLD activation and that the mitogenic activity of this vasoactive peptide on endometrial stromal cells may in part be mediated via the PLD pathway. This may have significance both to implantation and endometrial cancer.
Ahmed
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A
Centre for Clinical Research in Immunology and Signalling and Department of Obstetrics & Gynaecology, Medical School, University of Birmingham, Edgbaston, U.K.
Ferriani
R A
RA
Smith
S K
SK
D000328:Adult; D000470:Alkaloids / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019833:Genistein; D020404:Glycerophospholipids; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D008875:Middle Aged; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019311:Staurosporine; D017154:Stromal Cells; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D004791:Enzyme Inhibitors; D020404:Glycerophospholipids; D007295:Inositol Phosphates; D007529:Isoflavones; D010712:Phosphatidic Acids; C068564:phosphatidylbutanol; D004247:DNA; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin