title: 2-Aminoethyl diphenylborinate analogues: selective inhibition for store-operated Ca2+ entry.
abstract: Capacitative calcium entry (CCE), the mechanism that replenishes the internal Ca2+ stores with Ca2+ from the extracellular milieu in response to depletion of the store, is mediated by Ca2+ channels in the plasma membrane generally referred to as store-operated channels (SOCs). However, the roles of SOCs in the more physiological context have been fully elucidated. 2-Aminoethyl diphenylborinate (2-APB) strongly inhibits SOCs, as well as inositol-1,4,5 trisphosphate (IP3) receptors. In the present study, we screened a library of 166 2-APB analogues for effects on CCE and IP3-induced Ca2+ release in order to discover specific SOC inhibitors, and found that some blocked both store-operated and receptor-operated Ca2+ influx more strongly and selectively than 2-APB. Indeed, these new compounds ceased the prolonged intracellular Ca2+ oscillations induced by a low concentration of ATP in CHO-K1 cells. These novel SOC inhibitors will be valuable pharmacological and biochemical tools for elucidating the physiological roles.
authors.affiliation: The Division of Molecular Neurobiology, Institute of Medical Sciences, University of Tokyo, 4-6-1 Shirokanedai, Tokyo 108-8639, Japan.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Hirohide
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Maruyama
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hamano
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ozaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mizutani
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008657:Metabolic Clearance Rate / Q000187:drug effects
chemical_list: D001896:Boron Compounds; D015220:Calcium Channels; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium