Adenophostin A can stimulate Ca2+ influx without depleting the inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in the Xenopus oocyte

Sylvain DeLisle, Erik W. Marksberry, Carl Bonnett, David J. Jenkins, Barry V.L. Potter, Masaaki Takahashi, Kazuhiko Tanzawa

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Adenophostin A possesses the highest known affinity for the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) receptor (InsP3R). The compound shares with Ins(1,4,5)P3 those structural elements essential for binding to the InsP3R. However, its adenosine 2'-phosphate moiety has no counterpart in the Ins(1,4,5)P3 molecule. To determine whether its unique structure conferred a distinctive biological activity, we characterized the adenophostin-induced Ca2+ signal in Xenopus oocytes using the Ca2+-gated Cl- current assay. In high concentrations, adenophostin A released Ca2+ from Ins(1,4,5)P3- sensitive stores and stimulated a Cl- current that depended upon the presence of extracellular Ca2+. We used this Cl- current as a marker of Ca2+ influx. In low concentrations, however, adenophostin A stimulated Ca2+ influx exclusively. In contrast, Ins(1,4,5)P3 and (2-hydroxyethyl)- α-D-glucopyranoside 2',3,4-trisphosphate, an adenophostin A mimic lacking most of the adenosine moiety, always released intracellular Ca2+ before causing Ca2+ influx. Ins(1,4,5)P3 could still release Ca2+ during adenophostin A-induced Ca2+ influx, confirming that the Ins(1,4,5)P3- sensitive intracellular Ca2+ stores had not been emptied. Adenophostin- and Ins(1,4,5)P3-induced Ca2+ influx were not additive, suggesting that both agonists stimulated a common Ca2+ entry pathway. Heparin, which blocks binding to the InsP3R, prevented adenophostin-induced Ca2+ influx. These data indicate that adenophostin A can stimulate the influx of Ca2+ across the plasma membrane without inevitably emptying the Ins(1,4,5)P3-sensitive intracellular Ca2+ stores.

Original languageEnglish (US)
Pages (from-to)9956-9961
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number15
DOIs
StatePublished - Apr 11 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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