Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca²⁺] in Rat Mesenteric Lymphatic Vessels.
Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca²⁺] in Rat Mesenteric Lymphatic Vessels.
复制标题
急性酒精中毒诱导的大鼠肠系膜淋巴管中 [Ca²α] 循环动员的调节机制。
DOI：
10.1089/lrb.2014.0048
复制
发表时间：
2015
影响因子：
1.4
通讯作者：
Molina,PatriciaE
中科院分区：
文献类型：
--
作者：
Souza-Smith,FlaviaM;Kerut,EdmundK;Breslin,JeromeW;Molina,PatriciaE
背景：我们已经证明，急性酒精中毒（AAI）增加泵淋巴管中钙瞬变的幅度。我们测试的贡献胞外Ca 2+通过L-型Ca 2+通道和胞内Ca 2+释放肌浆网（SR）AAI诱导的增加Ca 2 +transients.Methods和结果：AAI产生由灌胃给药的30%酒精清醒，不受约束的大鼠;等容管理水作为对照。分离肠系膜淋巴管，插管，并加载Fura-2 AM，以测量细胞内Ca 2+的变化。在2、6和10 cm H2O的管腔内压力下进行测量。硝苯地平阻断L-型钙通道; xestospongin C抑制IP-3受体;咖啡因实现SR Ca 2+释放和Ca 2+池（无Ca 2 + APSS）。硝苯地平在所有压力下都能降低AAI和对照组的淋巴管Ca 2+瞬时幅度，但仅在对照组中降低淋巴管收缩频率。Xestospongin C并没有显着改变任何的Ca 2+参数在任何一组，但是，分数缩短增加在低透壁压的控制。RyR（ryanodine受体）激活与咖啡因导致一个单一的收缩与更大的Ca 2+瞬态AAI比那些从对照组的arrhatics。结论：1）AAI引起的淋巴管钙瞬变增加与L型钙通道有关，2）阻断IP-3受体可增加淋巴管对钙的敏感性，3）AAI增加淋巴管SR内钙贮量。
Background:We have demonstrated that acute alcohol intoxication (AAI) increases the magnitude of Ca2+transients in pumping lymphatic vessels. We tested the contribution of extracellular Ca2+via L-type Ca2+channels and intracellular Ca2+release from the sarcoplasmic reticulum (SR) to the AAI-induced increase in Ca2+transients.Methods and Results:AAI was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats; isovolumic administration of water served as the control. Mesenteric lymphatic vessels were isolated, cannulated, and loaded with Fura-2 AM to measure changes in intracellular Ca2+. Measurements were made at intraluminal pressures of 2, 6, and 10 cm H2O. L-type Ca2+channels were blocked with nifedipine; IP-3 receptors were inhibited with xestospongin C; and SR Ca2+release and Ca2+pool (Ca2+free APSS) were achieved using caffeine. Nifedipine reduced lymphatic Ca2+transient magnitude in both AAI and control groups at all pressures tested, but reduced lymphatic contraction frequency only in the control group. Xestospongin C did not significantly change any of the Ca2+parameters in either group; however, fractional shortening increased in the controls at low transmural pressure. RyR (ryanodine receptor) activation with caffeine resulted in a single contraction with a greater Ca2+transient in lymphatics from AAI than those from controls. SR Ca2+pool was also greater in lymphatics isolated from AAI- than from control animals.Conclusions:These data suggest that 1) L-type Ca2+channels contribute to the AAI-induced increase in lymphatic Ca2+transient, 2) blockage of IP-3 receptors could increase calcium sensitivity, and 3) AAI increases Ca2+storage in the SR in lymphatic vessels.