title: Antagonistic effect of inositol pentakisphosphate on inositol triphosphate receptors.
abstract: We present evidence that inositol 1,3,4,5,6-pentakisphosphate acts as an antagonist of inositol triphosphate receptors in vitro by dampening the activity of Ca(2+)-mobilizing inositol phosphates. This antagonism bears physiological significance as cells maintain substantial quantities of this phosphoinositol in the cytosol, especially during cell differentiation or proliferation. Over a concentration range from 30 to 150 microM, this pentakisphosphate causes a two- to five-fold increase in the EC50 values of inositol 1,4,5-trisphosphate and other active phosphoinositols in effecting Ca2+ efflux from brain microsomes. This specific inhibition results from competitive receptor binding, and is not noted with inositol hexaphosphate or related metabolites at comparable concentrations. Thus, inositol 1,3,4,5,6-pentakisphosphate in concert with other allosteric modulators may constitute an integral component for the receptor regulation.
authors.affiliation: Division of Medical Chemistry & Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Lu
authors.forename: W R
authors.initials: WR
authors.lastname: Shieh
authors.forename: C S
authors.initials: CS
authors.lastname: Chen
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D018160:Receptors, Cytoplasmic and Nuclear; C013571:inositol pentaphosphate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium