Liepins A, LeFever A, Truitt R L
Memorial University, Faculty of Medicine, St. John's, Newfoundland, Canada.
Immunopharmacol Immunotoxicol. 1989;11(2-3):165-78. doi: 10.3109/08923978909005363.
Potassium channel activity has been implicated in the lytic function of cloned murine effector T lymphocytes (5) and human NK cells (12) as well as in the initiation of the injury process in tumor cells (23). In the present studies, the effects of various K+ channel blockers on the cytolytic function of in vivo derived alloimmune lymphocytes towards P815 tumor cells were evaluated. The classical K+ channel blocker 4-aminopyridine (4-AP), the naturally occurring monoamine serotonin (5-hydroxytryptamine, 5-HT) and its agonist, quipazine, as well as the Ca++ dependent K+ channel blocker quinidine were chosen for investigation based on their known ion channel gating properties. These agents, when present in the assay medium, inhibited in a dose dependent manner the lysis of P815 tumor cells as measured by specific 51Cr release. Preincubation of effector lymphocytes with the various K+ channel blockers resulted in greater inhibition of lysis than did the preincubation of target cells. The 5-HT agonist quipazine was of particular interest in that it inhibited the lytic process with equal effectiveness when continuously present in the assay medium or when the effector cells alone were preincubated. Quinidine was used to investigate whether Ca++ dependent K+ channels were the predominant ion channel involved in the lytic process. When present during the lytic assay, quinidine was similar to quipazine in terms of their dose range at which they inhibited the lytic process. These results indicate that 5-HT sensitive Ca++ dependent K+ channels are likely to be involved in the delivery of lytic signal(s) by immune effector lymphocytes and suggests that neuroendocrine products may modulate the functional activity of in vivo derived lymphocytes.
钾通道活性与克隆的小鼠效应T淋巴细胞（5）和人自然杀伤细胞（12）的溶解功能有关，也与肿瘤细胞损伤过程的起始有关（23）。在本研究中，评估了各种钾通道阻滞剂对体内产生的同种免疫淋巴细胞针对P815肿瘤细胞的细胞溶解功能的影响。基于其已知的离子通道门控特性，选择了经典的钾通道阻滞剂4-氨基吡啶（4-AP）、天然存在的单胺血清素（5-羟色胺，5-HT）及其激动剂喹哌嗪，以及钙依赖性钾通道阻滞剂奎尼丁进行研究。当这些试剂存在于测定培养基中时，它们以剂量依赖性方式抑制通过特异性51Cr释放测量的P815肿瘤细胞的溶解。效应淋巴细胞与各种钾通道阻滞剂预孵育比靶细胞预孵育导致更大程度的溶解抑制。5-HT激动剂喹哌嗪特别令人感兴趣，因为当它持续存在于测定培养基中或仅效应细胞预孵育时，它以相同的效力抑制溶解过程。使用奎尼丁研究钙依赖性钾通道是否是参与溶解过程的主要离子通道。在溶解测定期间存在时，奎尼丁在抑制溶解过程的剂量范围方面与喹哌嗪相似。这些结果表明，5-HT敏感的钙依赖性钾通道可能参与免疫效应淋巴细胞的溶解信号传递，并表明神经内分泌产物可能调节体内产生的淋巴细胞的功能活性。
