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Effects of Adenophostin-A and Inositol-1,4,5-trisphosphate on Cl − Currents in Xenopus laevis Oocytes

Molecular Pharmacology, ISSN: 0026-895X, Vol: 51, Issue: 4, Page: 683-692
1997
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Article Description

Adenophostin-A, a novel compound isolated from cultures of Penicillium brevicompactum, has been shown to stimulate Ca 2+ release from inositol-1,4,5-trisphosphate (IP 3 )-sensitive Ca 2+ stores in microsomal preparations, permeabilized cells, and lipid vesicles containing purified IP 3 receptor. The purpose of the current study was to compare the effects of adenophostin-A and IP 3 on Ca 2+ release from stores and Ca 2+ influx in intact Xenopus laevis oocytes. Ca 2+ influx though store-operated Ca 2+ channels and Ca 2+ release from stores were monitored by measuring two Ca 2+ -activated Cl − currents that can be used as real-time indicators of Ca 2+ release and Ca 2+ influx (I Cl-1 and I Cl-2, respectively). We find that high concentrations (final intraoocyte concentrations of 5–10 μ m ) of adenophostin-A and IP 3 stimulate a large Ca 2+ release from stores (as measured by I Cl-1 ) followed by Ca 2+ influx (as measured by I Cl-2 ). Low concentrations (∼50 n m ) of IP 3 stimulate oscillations in Ca 2+ release without stimulating Ca 2+ influx. In contrast, low concentrations of adenophostin-A can stimulate Ca 2+ influx without stimulating a large Ca 2+ release. However, Ca 2+ influx did not occur in the complete absence of Ca 2+ release. Therefore, it is unlikely that adenophostin-A directly stimulates store-operated Ca 2+ channels. We hypothesize that adenophostin-A releases Ca 2+ from a subpopulation of stores that is tightly coupled to store-operated Ca 2+ channels.

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