title: Comparative studies of D-myoinositol 1,4,5-trisphosphate and synthetic 6-deoxy D-myoinositol 1,4,5-trisphosphate: binding and calcium release activity in rat parotid microsomes.
abstract: In this study, we report our data on the binding of D-myoinositol(1,4,5)P3 and of 6-deoxy D-myoinositol(1,4,5)P3 to a rat parotid microsomal fraction and their effect on Ca2+ release. The binding affinity and the potency of 6-deoxy Ins(1,4,5)P3 to induce Ca2+ release are about 100 times lower than those of Ins(1,4,5)P3. However, maximal concentrations of both inositol trisphosphates induce similar calcium efflux and present comparable displacement of radioligand binding. Experiments were performed to exclude that the microsomal preparations used display rapid metabolism of Ins(1,4,5)P3 or 6-deoxy Ins(1,4,5)P3 during binding and Ca2+ release. We also report that, in permeabilized rat parotid acini preparations, 6-deoxy Ins(1,4,5)P3 is about 100 times less potent than Ins(1,4,5)P3 in inducing Ca2+ release. These data indicate that removal of the hydroxyl group in position 6 of the Ins(1,4,5)P3 molecule severely reduces its binding affinity which seems, in a large part at least, responsible for the reported loss of potency in mobilizing Ca2+. Nevertheless, 6-deoxy Ins(1,4,5)P3 seems to be a full agonist for the release of Ca2+.
authors.affiliation: Biochimie des transports cellulaires (CNRS URA 1116), Orsay, France.
authors.forename: D
authors.initials: D
authors.lastname: Bonis
authors.forename: A
authors.initials: A
authors.lastname: Sezan
authors.forename: P
authors.initials: P
authors.lastname: Mauduit
authors.forename: D
authors.initials: D
authors.lastname: Dubreuil
authors.forename: J
authors.initials: J
authors.lastname: Cleophax
authors.forename: S D
authors.initials: SD
authors.lastname: Gero
authors.forename: B
authors.initials: B
authors.lastname: Rossignol
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D004305:Dose-Response Relationship, Drug; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D010306:Parotid Gland / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; C067150:6-deoxyinositol 1,4,5-triphosphate; D015544:Inositol 1,4,5-Trisphosphate; D010744:Phosphoric Monoester Hydrolases; C043422:myo-inositol 1,4,5-triphosphate phosphatase; D002118:Calcium