The effects of Ca2(+)-antagonists, especially nifedipine, on contraction and increase of intracellular Ca2+ (Fura-2/AM method) evoked by ATP were evaluated in a thin outer layer segment of guinea-pig urinary bladder. 2. The ATP-evoked contraction was markedly inhibited by dihydropyridine-type Ca2(+)-antagonists, such as nifedipine and nitrendipine, but not by D-600, omega-conotoxin and tetramethrin. 3. This antagonism by nifedipine of ATP-evoked contractions was competitive from the Schild plot analysis, the pA2 value being 8.23. The reduction of ATP-evoked contraction by nifedipine (0.1 microM) was fully reversed by administration of Bay K 8644 (0.1 microM). 4. ATP (100 microM) caused an increase of fluorescence brightness after loading Fura-2/AM, which was coupled with a contraction of the bladder. Both the contraction and the elevation of intracellular Ca2+ evoked evoked by the nucleotide were completely antagonized by nifedipine. by the nucleotide were completely antagonized by nifedipine. 5. These results suggest that ATP may activate the dihydropyridine-sensitive, voltage-dependent Ca2(+)-channels in a direct or indirect fashion and, thereby, elicit a contraction of the bladder.
摘要
在豚鼠膀胱薄外层段中，评估了Ca2+拮抗剂，尤其是硝苯地平，对ATP诱发的收缩及细胞内Ca2+增加（Fura-2/AM法）的影响。2. 二氢吡啶类Ca2+拮抗剂，如硝苯地平和尼群地平，可显著抑制ATP诱发的收缩，但D-600、ω-芋螺毒素和胺菊酯则无此作用。3. 从Schild图分析可知，硝苯地平对ATP诱发收缩的这种拮抗作用具有竞争性，pA2值为8.23。给予Bay K 8644（0.1μM）可完全逆转硝苯地平（0.1μM）对ATP诱发收缩的抑制作用。4. ATP（100μM）在加载Fura-2/AM后可引起荧光亮度增加，这与膀胱收缩相关。核苷酸诱发的收缩和细胞内Ca2+升高均被硝苯地平完全拮抗。5. 这些结果表明，ATP可能以直接或间接方式激活二氢吡啶敏感的电压依赖性Ca2+通道，从而引发膀胱收缩。
