The nature and mechanism of activation of the hepatocyte receptor-activated Ca2+ inflow system

Greg J. Barritt, Bernard P. Hughes

    Research output: Contribution to journalShort surveypeer-review

    28 Citations (Scopus)

    Abstract

    Progress in elucidation of the properties of the hepatocyte receptor-activated Ca2+ inflow system (RACIS) has been hampered by difficulties in measuring rates of Ca2+ inflow to hepatocytes. These difficulties have led, for example, to different conclusions about the relationship between the extracellular Ca2+ concentration and the movement of Ca2+ through the RACIS. The hepatocyte RACIS admits Mn2+ and a number of other divalent cations as well as Ca2+. Many of these cations also inhibit the movement of Ca2+ through this system. While the RACIS is inhibited by high concentrations of verapamil and by some other Ca2+ antagonists, it is relatively insensitive to inhibition by organic compounds which inhibit other Ca2+ channels and Ca2+ transporters. There is circumstantial evidence which suggests that the hepatocute RACIS is an exchange system, possibly one which catalyses Ca2+-H+ exchange or the co-transport of Ca2+ and OH-. Other circumstantial evidence suggests that the RACIS is a channel, with some similarities to voltage-operated Ca2+ channels in excitable cells. However, experiments using the patch-clamp technique have not yet detected agonist-stimulated Ca2+ movement across the hepatocyte plasma membrane. The molecular components of the RACIS probably differ from those which facilitate the large inflow of Ca2+ to hepatocytes which occurs in the absence of an agonist. The mechanism by which agonists activate the RACIS has not been elucidated. It may involve the binding of inositol 1,4,5-trisphosphate and/or inositol 1,3,4,5-tetrakisphosphate to an allosteric site on the putative Ca2+ channel, the direct interaction of a pertussis toxin-sensitive G protein, Gi2 or Gi3, with the putative Ca2+ channel and/or an unknown signal transmitted to the putative channel when the inositol 1,4,5-trisphosphate-sensitive Ca2+ store (the endoplasmic reticulum) is emptied.

    Original languageEnglish
    Pages (from-to)283-292
    Number of pages10
    JournalCellular Signalling
    Volume3
    Issue number4
    DOIs
    Publication statusPublished - 1991

    Keywords

    • Ca
    • channel
    • GTP-binding proteins
    • hepatocyte
    • inositol 1,4,5-trisphosphate
    • Mn

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