Opening of Ca2+-Dependent K+ Channels by Nordihydroguaiaretic Acid in Porcine Coronary Arterial Smooth Muscle Cells

Mechanisms Underlying the Activation of Large Conductance Ca2+-Activated K+ Channels by Nordihydroguaiaretic Acid

“…The increase in [Ca 2+ ]i by NDGA was not any artifacts due to the optical measurement, since it was also observed using other Ca 2+ indicators, fluo-4 and fura-2, and was markedly reduced by pretreatment with caffeine and ryanodine. The concentration of NDGA required for the significant Ca 2+ release (³30 mM) was apparently higher than that for the direct activation of BK channels (³3 m M) (12) ]i elevation in the junctional areas between the peripheral SR fragment and plasma membrane may be higher than 500 nM and, thereby, may induce a large current as observed. A similar assumption was proved for the Ca 2+ release from the peripheral SR fragment by NS-1619 (21).…”

“…The inhibition of mitochondria respiration by high concentrations of NDGA has been also reported (10,11). We found that the application of NDGA directly enhanced single BK channel activity in excised and on-cell patches of porcine coronary arterial smooth muscle cells (PCASMCs) (12). Moreover, the opening of BK channels by NDGA, which is independent of its lipoxygenase inhibition or antioxidant effect, results in membrane hyperpolarization in PCASMCs (13).…”

“…Our previous study showed that 10 mM NDGA increased P o of BK channels in inside-out patches of PCASMCs at pCa 7.0 and holding potential of 0 mV by about 30 times, indicating that NDGA directly opened the BK channel (12). Since the opening of BK channel by NDGA depended on the presence of Ca 2+ at concentrations higher than pCa 8.5, the effect might be due to the increase in Ca 2+ sensitivity of BK channels.…”

“…Our previous studies indicate that the potentiation of BK channel activity by NDGA is mediated by at least two different mechanisms; the direct activation of BK channels (12) and the enhancement of Ca 2+ release from intracellular storage sites (13). In the present study, whether NDGA acted on the a or b subunit of BK channel was examined using human embryonic kidney (HEK293) cell, where BK channel a subunit (BKa ) or both a and b1 subunits (BKab1) were as expressed by cDNA transfection.…”

Antigenotoxic effect of nordihydroguaiaretic acid against chlormadinone acetate-induced genotoxicity in mice bone-marrow cells

“…1) [1]. NDGA possesses a number of interesting biological properties which are of potential use to humans such as enzyme inhibition [2], antimicrobial properties [3], protection from neurotoxicity and bladder toxicity [4,5], stimulation of the corpus luteum for the secretion of progesterone [6], potential vaso-and bronchodilation [7], and anti-apoptotic [8], estrogenic [9], antimutagenic [10] and anti-cancer [11] properties. NDGA has also been reported to possess both genotoxic [12] and anti-genotoxic potential [13] in vivo and in vitro.…”