Bradykinin activates protein kinase C in cultured cortical collecting tubular cells.
Bradykinin inhibits vasopressin-stimulated water transport in cortical collecting tubular cells. The biochemical mechanism of this effect was explored by means of primary cultures of rabbit cortical collecting tubular cells. Bradykinin was found to produce a rapid release of calcium from intracellular stores, an increase in sn-1,2-diacylglycerol levels, and a fivefold increase in membrane-bound protein kinase C activity, consistent with stimulation of phospholipase C and activation of protein kinase C in rabbit cortical collecting tubular cells. In addition, bradykinin produced a dose-dependent 46% inhibition of vasopressin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation. Pretreatment with the protein kinase C inhibitors, H-7 and staurosporine, reversed the bradykinin-mediated inhibition of vasopressin-stimulated cAMP accumulation. In contrast, pretreatment with either the phospholipase A2 inhibitor, mepacrine, or pertussis toxin did not prevent the inhibitory effect of bradykinin on vasopressin-stimulated cAMP production, suggesting that the effects are not mediated by prostaglandin E2 or activation of a pertussis-toxin sensitive guanine nucleotide regulatory protein (e.g., Gi). Because bradykinin also inhibits isoproterenol-stimulated cAMP formation but does not inhibit either basal-, forskolin-, or cholera toxin-stimulated cAMP accumulation, the site of this inhibition appears to involve the hormone receptor or coupling of the receptor to the stimulatory guanine nucleotide regulatory subunit (Gs). The results demonstrate that bradykinin stimulates phospholipase C leading to activation of protein kinase C, which then inhibits vasopressin-stimulated cAMP production at the level of the hormone receptor or coupling of the receptor to Gs in cultured cortical collecting tubular cells.
Dixon
B S
BS
Department of Medicine, Veterans Administration Hospital, Denver, Colorado.
Breckon
R
R
Fortune
J
J
Sutherland
E
E
Simon
F R
FR
Anderson
R J
RJ
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D004075:Diglycerides; D004789:Enzyme Activation; D007425:Intracellular Membranes / Q000378:metabolism; D007684:Kidney Tubules / Q000201:enzymology*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology
C011439:1,2-diacylglycerol; D004075:Diglycerides; D011448:Prostaglandin Antagonists; D014667:Vasopressins; D000242:Cyclic AMP; D011493:Protein Kinase C; D001920:Bradykinin; D002118:Calcium