title: Characterisation of a novel Ca2+ pump inhibitor (bis-phenol) and its effects on intracellular Ca2+ mobilization.
abstract: Bis-phenol, a phenolic antioxidant, is an inhibitor of sarcoplasmic reticulum (SR), endoplasmic reticulum (ER) and plasma membrane Ca2+ ATPases. The concentration of bis-phenol giving half-maximal inhibition of the SR Ca(2+)-ATPase is 2 microM. On binding to the SR Ca(2+)-ATPase it shifts the E2 to E1 transition towards the E2 state and slows the transition between E2 to E1. Bis-phenol completely inhibits Ca(2+)-dependent ATP hydrolysis and Ca2+ uptake by rat cerebellar microsomes at a concentration of 30 microM. The plasma membrane Ca(2+)-ATPase is also completely inhibited at similar concentrations, however, the Na+/K(+)-ATPase is only marginally affected. Other inhibitors of the ER Ca(2+)-ATPases, thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone (BHQ), inhibit Ca2+ uptake by approximately 75%. Bis-phenol therefore inhibits all types of ER Ca(2+)-ATPases present in cerebellum. This inhibitor is also able to mobilize Ca2+ from intracellular Ca2+ stores, including those sensitive to InsP3, in intact HL-60 cells.
authors.affiliation: School of Biochemistry, University of Birmingham, Edgbaston, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Brown
authors.forename: S L
authors.initials: SL
authors.lastname: Benyon
authors.forename: C J
authors.initials: CJ
authors.lastname: Kirk
authors.forename: M
authors.initials: M
authors.lastname: Wictome
authors.forename: J M
authors.initials: JM
authors.lastname: East
authors.forename: A G
authors.initials: AG
authors.lastname: Lee
authors.forename: F
authors.initials: F
authors.lastname: Michelangeli
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D051381:Rats
chemical_list: D002084:Butylated Hydroxytoluene; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; C008437:2,2'-methylenebis(4-methyl-6-tert-butylphenol); D002118:Calcium