Effects of adenophostin-A and inositol-1,4,5-trisphosphate on Cl- currents in Xenopus laevis oocytes.
Adenophostin-A, a novel compound isolated from cultures of Penicillium brevicompactum, has been shown to stimulate Ca2+ release from inositol-1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores in microsomal preparations, permeabilized cells, and lipid vesicles containing purified IP3 receptor. The purpose of the current study was to compare the effects of adenophostin-A and IP3 on Ca2+ release from stores and Ca2+ influx in intact Xenopus laevis oocytes. Ca2+ influx though store-operated Ca2+ channels and Ca2+ release from stores were monitored by measuring two Ca2+ -activated Cl- currents that can be used as real-time indicators of Ca2+ release and Ca2+ influx (I(Cl-1) and I(Cl-2), respectively). We find that high concentrations (final intraoocyte concentrations of 5-10 microM) of adenophostin-A and IP3 stimulate a large Ca2+ release from stores (as measured by I(Cl-1)) followed by Ca2+ influx (as measured by I(Cl-2)). Low concentrations (approximately 50 nM) of IP3 stimulate oscillations in Ca2+ release without stimulating Ca2+ influx. In contrast, low concentrations of adenophostin-A can stimulate Ca2+ influx without stimulating a large Ca2+ release. However, Ca2+ influx did not occur in the complete absence of Ca2+ release. Therefore, it is unlikely that adenophostin-A directly stimulates store-operated Ca2+ channels. We hypothesize that adenophostin-A releases Ca2+ from a subpopulation of stores that is tightly coupled to store-operated Ca2+ channels.
Hartzell
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HC
Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322-3030, USA. criss@anatomy.emory.edu
Machaca
K
K
Hirayama
Y
Y
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D014982:Xenopus laevis
D015220:Calcium Channels; D018118:Chloride Channels; D002712:Chlorides; C085029:adenophostin A; D015544:Inositol 1,4,5-Trisphosphate; D000241:Adenosine; D002118:Calcium