Effects of adenophostin-A and inositol-1,4,5-trisphosphate on Cl- currents in Xenopus laevis oocytes

• Published in: Molecular pharmacology 1997-04, Vol.51 (4), p.683-692
• Main Authors: Hartzell, H C, Machaca, K, Hirayama, Y
• Format: Article
• Language: English
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Animals; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - metabolism; Chloride Channels - drug effects; Chloride Channels - metabolism; Chloride Channels - physiology; Chlorides - metabolism; Chlorides - physiology; Inositol 1,4,5-Trisphosphate - pharmacology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Oocytes - drug effects; Oocytes - metabolism; Xenopus laevis
• ISSN: 0026-895X; 1521-0111
• DOI: 10.1124/mol.51.4.683

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.