title: Generation of calcium oscillations in fibroblasts by positive feedback between calcium and IP3.
abstract: A wide variety of nonexcitable cells generate repetitive transient increases in cytosolic calcium ion concentration ([Ca2+]i) when stimulated with agonists that engage the phosphoinositide signalling pathway. Current theories regarding the mechanisms of oscillation disagree on whether Ca2+ inhibits or stimulates its own release from internal stores and whether inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG) also undergo oscillations linked to the Ca2+ spikes. In this study, Ca2+ was found to stimulate its own release in REF52 fibroblasts primed by mitogens plus depolarization. However, unlike Ca2+ release in muscle and nerve cells, this amplification was insensitive to caffeine or ryanodine and required hormone receptor occupancy and functional IP3 receptors. Oscillations in [Ca2+]i were accompanied by oscillations in IP3 concentration but did not require functional protein kinase C. Therefore, the dominant feedback mechanism in this cell type appears to be Ca2+ stimulation of phospholipase C once this enzyme has been activated by hormone receptors.
authors.affiliation: Howard Hughes Medical Institute M-047, University of California San Diego, La Jolla 92093-0647.
authors.forename: A T
authors.initials: AT
authors.lastname: Harootunian
authors.forename: J P
authors.initials: JP
authors.lastname: Kao
authors.forename: S
authors.initials: S
authors.lastname: Paranjape
authors.forename: R Y
authors.initials: RY
authors.lastname: Tsien
mesh_terms: D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D005246:Feedback; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D010507:Periodicity; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D012433:Ryanodine; D015240:Phorbol 12,13-Dibutyrate; D002110:Caffeine; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium