Nikodijevic B, Nikodijevic-Kedeva D, Oshima M, Paige B, Guroff G
Section on Growth Factors, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
J Neurosci Res. 1994 Jan;37(1):71-82. doi: 10.1002/jnr.490370110.
Treatment of PC12 cells with Bay K 8644 for 12 hr or more leads to an almost 80% decrease in the subsequent ability of Bay K 8644 to stimulate the uptake of radioactive calcium into the cells. This effect is a property of the S(-)isomer of Bay K 8644; pre-treatment with the R(+)isomer, now known to be a calcium channel blocker, has the opposite effect. This treatment is specific in that it does not interfere with the stimulation of calcium uptake by potassium, ATP, or nerve growth factor. Such treatment is accompanied by a 90% decrease in the ability of Bay K 8644 to stimulate the release of norepinephrine. The characteristics of the binding of [3H]isradipine to control and to treated cells indicates that the decrease in the effect of dihydropyridines is accompanied by a marked decrease in the number of dihydropyridine binding sites with no apparent change in the affinity of the remaining sites. The continued ability of depolarizing levels of potassium to stimulate calcium uptake and the induction of the protooncogene c-fos in Bay K 8644-treated cells indicates that the L-type calcium channels are still intact, but are simply unresponsive to dihydropyridine agonists.
用Bay K 8644处理PC12细胞12小时或更长时间，会导致Bay K 8644随后刺激放射性钙摄入细胞的能力下降近80%。这种效应是Bay K 8644的S(-)异构体所特有的；用现在已知为钙通道阻滞剂的R(+)异构体进行预处理则产生相反的效果。这种处理具有特异性，因为它不会干扰钾、ATP或神经生长因子对钙摄入的刺激。这种处理伴随着Bay K 8644刺激去甲肾上腺素释放的能力下降90%。[3H]异搏定与对照细胞和处理后细胞结合的特性表明，二氢吡啶作用的降低伴随着二氢吡啶结合位点数量的显著减少，而其余位点的亲和力没有明显变化。钾去极化水平持续刺激钙摄入以及在Bay K 8644处理的细胞中诱导原癌基因c-fos，表明L型钙通道仍然完好，但只是对二氢吡啶激动剂无反应。
