title: Regulation of the type III InsP(3) receptor by InsP(3) and calcium.
abstract: It has been proposed that the inositol 1,4,5-trisphosphate receptor (InsP(3)R) type III acts as a trigger for InsP(3)-mediated calcium (Ca(2+)) signaling, because this InsP(3) isoform lacks feedback inhibition by cytosolic Ca(2+). We tested this hypothesis in RIN-m5F cells, which express predominantly the type III receptor. Extracellular ATP increases Ca(2+) in these cells, and we found that this effect is independent of extracellular Ca(2+) but is blocked by the InsP(3)R antagonist heparin. There was a dose-dependent increase in the number of cells responding to ATP and two-photon flash photolysis of caged-Ca(2+) heightened the sensitivity of RIN-m5F cells to this increase. These findings provide evidence that Ca(2+) increases the sensitivity of the InsP(3)R type III in intact cells and supports the idea that this isoform can act as a trigger for hormone-induced Ca(2+) signaling.
authors.affiliation: Department of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Allison F
authors.initials: AF
authors.lastname: O'Neill
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hagar
authors.forename: Warren R
authors.initials: WR
authors.lastname: Zipfel
authors.forename: Michael H
authors.initials: MH
authors.lastname: Nathanson
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Ehrlich
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010782:Photolysis; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D006493:Heparin; D002118:Calcium