PMID- 1282721 OWN - NLM STAT- MEDLINE DCOM- 19930211 LR - 20191028 IS - 1011-6524 (Print) IS - 1011-6524 (Linking) VI - 15 IP - 6 DP - 1992 Nov-Dec TI - Effect of bradykinin on the cytosolic free calcium activity and phosphoinositol turnover in human glomerular epithelial cells. PG - 277-88 AB - The effect of bradykinin (BK) on the intracellular free calcium activity [Ca2+]i and phosphoinositide (PI) turnover was investigated in human glomerular epithelial cells (GEC) in culture. Human GEC exhibited a baseline [Ca2+]i of 114 +/- 3 nmol (n = 81). BK (ED50 10(-9) mol/l) caused a rapid and transient increase in [Ca2+]i, which could also be observed in the absence of extracellular calcium. The effect of BK (10(-8) mol/l) on the [Ca2+]i was inhibited by the BK2 antagonist Hoe 140 (IC50 10(-8) mol/l). BK also induced PI turnover in a time- and dose-dependent manner. A transient increase in (1,4,5)-inositol-triphosphate (InsP3) formation from 1,445 +/- 119 to 4,629 +/- 323 cpm occurred after 5 s. Stimulation of protein kinase C (PKC) by short-term preincubation (15 min) of human GEC with phorbol-12-myristate-13-acetate (PMA) induced a dose-dependent inhibition of the BK-stimulated (10(-7) mol/l) inositol-phosphate formation. Downregulation of PKC by preincubation of human GEC with PMA (24 h, 10(-6) mol/l) or inhibition of PKC by pretreatment with staurosporin (1 h, 10(-6) mol/l) resulted in a slight but significant augmentation of the BK-induced InsP3 stimulation. The data indicate that BK induces stimulation of [Ca2+]i and PI turnover via a BK2 receptor in human GEC. PKC might exert a negative feedback function for the BK-induced PI turnover. FAU - Pavenstadt, H AU - Pavenstadt H AD - Department of Medicine, University of Freiburg, FRG. FAU - Spath, M AU - Spath M FAU - Fiedler, C AU - Fiedler C FAU - Fischer, R AU - Fischer R FAU - Schlunck, G AU - Schlunck G FAU - Wanner, C AU - Wanner C FAU - Schollmeyer, P AU - Schollmeyer P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Ren Physiol Biochem JT - Renal physiology and biochemistry JID - 8906670 RN - 0 (Phosphatidylinositols) RN - 7PG89G35Q7 (icatibant) RN - EC 2.7.11.13 (Protein Kinase C) RN - S8TIM42R2W (Bradykinin) RN - SY7Q814VUP (Calcium) SB - IM MH - Bradykinin/analogs & derivatives/antagonists & inhibitors/*pharmacology MH - Calcium/*metabolism MH - Cells, Cultured MH - Cytosol/drug effects/*metabolism MH - Epithelial Cells MH - Epithelium/drug effects/metabolism MH - Feedback MH - Humans MH - Kidney Glomerulus/cytology/*drug effects/metabolism MH - Phosphatidylinositols/*metabolism MH - Protein Kinase C/metabolism MH - Signal Transduction EDAT- 1992/11/01 00:00 MHDA- 1992/11/01 00:01 CRDT- 1992/11/01 00:00 PHST- 1992/11/01 00:00 [pubmed] PHST- 1992/11/01 00:01 [medline] PHST- 1992/11/01 00:00 [entrez] AID - 10.1159/000173464 [doi] PST - ppublish SO - Ren Physiol Biochem. 1992 Nov-Dec;15(6):277-88. doi: 10.1159/000173464.