Adenophostin A can stimulate Ca2+ influx without depleting the inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in the Xenopus oocyte
DeLisle, S., Marksberry, E. W., Bonnett, C., Jenkins, D. J., Potter, B. V. L., Takahashi, M. and Tanzawa, K., 1997. Adenophostin A can stimulate Ca2+ influx without depleting the inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in the Xenopus oocyte. Journal of Biological Chemistry, 272 (15), pp. 9956-9961.
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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.
|Creators||DeLisle, S., Marksberry, E. W., Bonnett, C., Jenkins, D. J., Potter, B. V. L., Takahashi, M. and Tanzawa, K.|
|Departments||Faculty of Science > Pharmacy & Pharmacology|
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