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The effect of 2,6-diisopropylphenol on the release of adenosine triphosphate in human erythrocytes.

机译：2，6-二异丙基苯酚对人红细胞中三磷酸腺苷释放的影响。

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摘要

The nucleotide adenosine triphosphate (ATP) has long been known to drive and participate in countless intracellular processes. One of these processes is ATP's ability to function as a powerful vasodilator. It has been well established that isolated healthy human erythrocytes (RBCs) release ATP when exposed to a hypoxic/hypercarbic environment. Propofol is the most common intravenously administered anesthetic in the United States and is known to cause a dose-dependent decrease in blood pressure. Differing hypotheses exist as to the exact mechanism of this drug-induced hypotension. A literature review demonstrates the variety of these hypotheses, some of which include: direct vasodilation, myocardial depression, and blunting of the baroreceptor reflex. This research study investigates the potential release of ATP from RBCs upon exposure to Propofol's active ingredient 2,6-diisopropylphenol. One mechanism of Propofol-induced hypotension may include the release of ATP from RBCs when exposed to 2,6-diisopropylphenol.;METHODS: RBCs were obtained from a donor. The RBCs were washed and then resuspended and diluted 1/1000 in Krebs-Henseleit solution. This process served to isolate the RBCs and enabled the researchers to perform manual counting. All samples were maintained at a temperature of 37° C through incubation and exposed to 2,6-diisopropylphenol for a range of 2 to 10 minutes. RBC counts were performed on each test and control group prior to testing. Test-group RBCs were then exposed to calculated doses of 2,6-diisoprophylphenol which were representative of differing plasma concentrations of Propofol. Both control and test groups were assayed using the Adenosine 5'-triphosphate Bioluminescent Assay Kit (Sigma) to determine if erythrocytes exposed to 2,6-diisopropylphenol released a greater amount of ATP than the control RBCs. Post-testing RBC counts were preformed to determine if cell lysis had occurred.;RESULTS: Results indicated a significant increase (p < 0.05) in ATP release from RBCs exposed to induction dose concentrations (50 ?g/ml) of 2,6-diisopropylphenol in vitro. The amount of ATP released in these experiments extrapolates to a physiologic concentration comparable to 10-6 M, which has previously been shown to result in maximal vasodilation. Statistical comparison of pre- and post-test RBC counts showed no significant difference (p > 0.05), thus ruling out RBC lysis as a source of the increased extracellular ATP.;CONCLUSION: The results of this research imply that an unexplored mechanism for the dose-dependent hypotension produced by the anesthetic agent propofol may exist. It was found that 2,6-diisopropylphenol, the active ingredient in propofol, significantly increases the release of ATP from human RBCs in vitro. It is possible that this increased release of ATP may result in the vasodilation and hypotension seen when propofol is administered in bolus dose concentrations, such as during anesthetic induction. Additional research including in vivo testing would be necessary to confirm this hypothesis.
机译：长期以来，核苷酸三磷酸腺苷（ATP）可以驱动并参与无数的细胞内过程。这些过程之一是ATP发挥强大血管扩张剂作用的能力。众所周知，当暴露于低氧/高碳环境中时，孤立的健康人红细胞（RBC）会释放ATP。丙泊酚是美国最常见的静脉内麻醉药，已知会引起血压的剂量依赖性降低。关于这种药物引起的低血压的确切机制存在不同的假设。文献综述证明了这些假设的多样性，其中包括：直接血管舒张，心肌抑制和压力感受器反射减弱。这项研究研究了丙泊酚活性成分2,6-二异丙基苯酚暴露后RBC中ATP的潜在释放。丙泊酚诱导的低血压的一种机制可能包括当暴露于2,6-二异丙基苯酚时从RBC中释放ATP。方法：RBC从供体获得。洗涤红细胞，然后重悬并在Krebs-Henseleit溶液中稀释1/1000。此过程有助于隔离RBC，并使研究人员能够执行手动计数。通过孵育将所有样品保持在37℃的温度下，并暴露于2，6-二异丙基苯酚2至10分钟。在测试之前，对每个测试和对照组进行RBC计数。然后将测试组的RBC暴露于计算出的2,6-二异丙基苯酚剂量，该剂量代表不同的丙泊酚血浆浓度。对照组和测试组均使用5'-三磷酸腺苷生物发光分析试剂盒（Sigma）进行分析，以确定暴露于2,6-二异丙基苯酚的红细胞释放的ATP是否比对照RBC释放的ATP量更大。结果：结果表明，暴露于诱导剂量浓度为2,6-（50μg/ ml）（50μg/ ml）的RBC中，ATP释放量显着增加（p <0.05）。体外使用二异丙基苯酚。在这些实验中释放的ATP的量外推至相当于10-6 M的生理浓度，以前已证明可导致最大的血管舒张。测试前和测试后RBC计数的统计比较显示无显着差异（p> 0.05），因此排除了RBC裂解是增加的细胞外ATP的来源。；结论：这项研究的结果表明，该机制尚待探索。可能存在麻醉药丙泊酚产生的剂量依赖性低血压。发现异丙酚中的活性成分2,6-二异丙基苯酚可显着增加体外人红细胞的ATP释放。 ATP的这种增加释放可能会导致以浓注剂量（例如在麻醉诱导期间）给予异丙酚时所见的血管舒张和低血压。包括体内测试在内的其他研究对于确认该假设是必要的。

著录项

  • 作者

    Chamberlain, Joseph C.;

  • 作者单位

    Webster University.;

  • 授予单位 Webster University.;
  • 学科 Pharmaceutical sciences.;Biochemistry.;Health sciences.
  • 学位 M.S.
  • 年度 2015
  • 页码 66 p.
  • 总页数 66
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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