Second-Generation Histamine H1 Receptor Antagonists Suppress Delayed Rectifier K+-Channel Currents in Murine Thymocytes
Second-Generation Histamine H1 Receptor Antagonists Suppress Delayed Rectifier K+-Channel Currents in Murine Thymocytes
复制标题
第二代组胺 H1 受体拮抗剂抑制小鼠胸腺细胞中的延迟整流 K 通道电流
DOI：
10.1155/2019/6261951
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发表时间：
2019
影响因子：
--
通讯作者：
Kazama I
中科院分区：
文献类型：
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作者：
Saito K;Abe N;Toyama H;Ejima Y;Yamauchi M;Mushiake H;Kazama I
背景/目标。电压依赖性钾通道(Kv1.3)主要表达在淋巴细胞膜上。这些通道对淋巴细胞的激活和增殖至关重要。由于第二代抗组胺药物具有亲脂性和免疫调节作用，因此它们被认为影响淋巴细胞的Kv1.3通道电流。采用小鼠胸腺细胞膜片钳全细胞记录技术，检测第二代抗组胺药物西替利嗪、非索非那定、氮卓斯汀和特非那定对小鼠胸腺细胞通道电流和膜电容的影响。氮卓斯汀和特非那定对通道峰电流和脉末电流的抑制作用比西替利嗪和非索非那定更明显。氮卓斯汀和特非那定均显著降低膜电容。由于这些药物不影响淋巴细胞的内吞过程，因此它们被认为与血浆膜直接相互作用。我们的研究首次揭示了第二代抗组胺药物，包括西替利嗪、非索非那定、氮卓斯汀和特非那定，对淋巴细胞Kv1.3-通道产生抑制作用。这些药物的疗效可能与其减少炎性细胞因子合成的免疫调节机制有关。
Background/Aims. Voltage‐dependent potassium channels (Kv1.3) are predominantly expressed in lymphocyte plasma membranes. These channels are critical for the activation and proliferation of lymphocytes. Since second‐generation antihistamines are lipophilic and exert immunomodulatory effects, they are thought to affect the lymphocyte Kv1.3‐channel currents.Methods. Using the patch‐clamp whole‐cell recording technique in murine thymocytes, we tested the effects of second‐generation antihistamines, such as cetirizine, fexofenadine, azelastine, and terfenadine, on the channel currents and the membrane capacitance.Results. These drugs suppressed the peak and the pulse‐end currents of the channels, although the effects of azelastine and terfenadine on the peak currents were more marked than those of cetirizine and fexofenadine. Both azelastine and terfenadine significantly lowered the membrane capacitance. Since these drugs did not affect the process of endocytosis in lymphocytes, they were thought to have interacted directly with the plasma membranes.Conclusions. Our study revealed for the first time that second‐generation antihistamines, including cetirizine, fexofenadine, azelastine, and terfenadine, exert suppressive effects on lymphocyte Kv1.3‐channels. The efficacy of these drugs may be related to their immunomodulatory mechanisms that reduce the synthesis of inflammatory cytokine.