NORDIHYDROGUAIARETIC ACID INHIBITS VOLTAGE-ACTIVATED CA-2+ CURRENTS INDEPENDENTLY OF LIPOXYGENASE INHIBITION

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  • 1 October 1990
    • journal article
    • research article
    • Vol. 38  (4) , 524-530
Abstract
The effects of nordihydroguaiaretic acid (NDGA), a widely used lipoxygenase inhibitor, were examined on voltage-activated Ca2+ channel currents in GH3 and AtT-20 pituitary cells. NDGA (10-100 .mu.M) produced a reversible, dose-dependent inhibition of Ca2+ channel currents, with half-maximal inhibition occurring at 18.6 .mu.M. Inhibition by NDGA developed relatively slowly, did not exhibit use dependence or voltage dependence, and did not require access of NDGA to the extracellular domain of the Ca2+ channel. The maximum inhibition of macroscopic currents by 30 .mu.M NDGA was equivalent in the presence of 5 and 50 mM extracellular Ca2+ and 5 mM Ba2+. NDGA inhibited Ca2+ channel currents in excised, outside-out patches, in the absence of intra- and extracellular Ca2+ (with Ba2+ as the charge carrier), and following preincubation of the cells with the phospholipase A2 inhibitor 4-bromophenacylbromide. Of five other lipoxygenase inhibitors tested, only one inhibited Ca2+ currents. These results suggest that NDGA inhibits Ca2+ channel currents by a mechanism distinct from that of other known Ca2+ channel antagonists and that, when influx of Ca2+ through voltage-gated channels is involved, inhibition of Ca2+-dependent cell functions by NDGA (> 10 .mu.M) may be independent of effects on arachidonic acid metabolism.