Song S K, Suh B C, Lee H, Kim K T
Department of Life Science and Basic Science Research Center, Pohang University of Science and Technology, South Korea.
Eur J Pharmacol. 1997 Mar 19;322(2-3):265-73. doi: 10.1016/s0014-2999(96)00998-3.
We investigated the cross-talk between the histamine and ATP receptors in HL-60 human promyelocytes. While both histamine and extracellular ATP increase intracellular Ca2+ concentration ([Ca2+]i) we found that histamine treatment causes a decrease in the subsequent ATP-induced Ca2+ release from intracellular stores and Ca2+ influx from extracellular space. In addition, histamine also inhibited the subsequent ATP-induced inositol 1.4,5-trisphosphate (IP3) generation in a manner comparable to the Ca2+ release. However, histamine did not inhibit thapsigargin-induced Ca2+ release and influx, thus indicating that histamine does not directly inhibit the Ca2+ release-activated channel (CRAC). Ca2+ elevation induced by 2'- and 3'-O-(4-benzoylbenzoyl) ATP (BzATP), which does not produce IP3, was also inhibited by treatment with histamine, suggesting the presence of ATP-gated channels that are regulated by histamine. Treatment with dibutyryl cAMP or 8-bromo-cAMP inhibited the subsequent ATP-induced response similar to histamine. Moreover, the incubation of cells with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), a protein kinase A inhibitor abolished histamine's inhibitory effect on the ATP-induced [Ca2+]i rise and IP3 formation. These results suggest that histamine inhibits both ATP-induced IP3 production and ATP-activated channel opening, through protein kinase A activation.
我们研究了HL-60人早幼粒细胞中组胺和ATP受体之间的相互作用。虽然组胺和细胞外ATP均能增加细胞内Ca2+浓度（[Ca2+]i），但我们发现组胺处理会导致随后ATP诱导的细胞内钙库Ca2+释放和细胞外空间Ca2+内流减少。此外，组胺还以与Ca2+释放相当的方式抑制了随后ATP诱导的肌醇1,4,5-三磷酸（IP3）生成。然而，组胺并未抑制毒胡萝卜素诱导的Ca2+释放和内流，因此表明组胺不会直接抑制Ca2+释放激活通道（CRAC）。组胺处理也抑制了由2'-和3'-O-(4-苯甲酰苯甲酰基)ATP（BzATP）诱导的Ca2+升高，BzATP不会产生IP3，这表明存在受组胺调节的ATP门控通道。用二丁酰cAMP或8-溴-cAMP处理可抑制随后ATP诱导的反应，类似于组胺。此外，用蛋白激酶A抑制剂N-[2-(对溴肉桂氨基)乙基]-5-异喹啉磺酰胺（H89）孵育细胞可消除组胺对ATP诱导的[Ca2+]i升高和IP3形成的抑制作用。这些结果表明，组胺通过激活蛋白激酶A抑制ATP诱导的IP3产生和ATP激活通道开放。
