Mais D E, Lahr P D, Bosin T R
Toxicol Appl Pharmacol. 1984 Oct;76(1):1-8. doi: 10.1016/0041-008x(84)90023-1.
Platelets and serotonin (5-HT) have been increasingly implicated in the pathophysiological response to lung microvascular injury. These experiments were undertaken to study the effect of agents known to injure the pulmonary microvasculature on platelet function, i.e., 5-HT uptake kinetics. Mice were exposed to 100% normobaric oxygen (24 to 96 hr) or pretreated ip (3 to 24 hr) with paraquat dichloride (50 mg/kg), diquat dibromide (68 mg/kg), or alpha-naphthylthiourea (ANTU, 10 mg/kg). Mouse platelet 5-HT accumulation was described by a saturable uptake system, possessing high affinity and low capacity, acting in conjunction with passive diffusion. The kinetic constants for the saturable uptake system in control mice were Km 3.37 +/- 0.32 X 10(-7) M and Vmax 46.7 +/- 3.5 pmol 10(8) platelets-1 min-1. Exposure to oxygen for 24 hr resulted in an increased affinity, Km 1.91 +/- 0.67 X 10(-7) M, and a decreased Vmax, 20.0 +/- 5.0 pmol 10(8) platelets-1 4 min-1, with no change in the passive diffusion component. Pretreatment with paraquat (3 hr) produced similar changes (Km 1.71 +/- 0.27 X 10(-7) M and Vmax 15.8 +/- 1.6 pmol 10(8) platelets-1 4 min-1), while diquat and ANTU failed to alter the kinetics of platelet 5-HT uptake. These changes appeared to require a pulmonary toxicant capable of generating a flux of oxygen radicals, and were not due to either the presence of residual toxicant, the presence of an endogenous inhibitor in platelet-rich plasma, or changes in the platelet content of endogenous 5-HT. This study has shown that hyperoxia and paraquat affect platelet function, and suggests that this alteration may contribute to the pathophysiological response of the pulmonary microvasculature to injury produced by these agents.
血小板和血清素（5-羟色胺，5-HT）在肺微血管损伤的病理生理反应中所起的作用日益受到关注。开展这些实验是为了研究已知会损伤肺微血管的药物对血小板功能的影响，即5-HT摄取动力学。将小鼠暴露于100%常压氧气中（24至96小时），或腹腔注射给予百草枯二氯化物（50毫克/千克）、敌草快二溴化物（68毫克/千克）或α-萘基硫脲（ANTU，10毫克/千克）进行预处理（3至24小时）。小鼠血小板对5-HT的摄取可通过一个具有高亲和力和低容量的可饱和摄取系统来描述，该系统与被动扩散共同起作用。对照小鼠中可饱和摄取系统的动力学常数为Km 3.37±0.32×10⁻⁷M，Vmax 46.7±3.5皮摩尔/10⁸个血小板⁻¹分钟⁻¹。暴露于氧气24小时导致亲和力增加，Km为1.91±0.67×10⁻⁷M，Vmax降低，为20.0±5.0皮摩尔/10⁸个血小板⁻¹4分钟⁻¹，被动扩散成分无变化。用百草枯预处理（3小时）产生了类似的变化（Km 1.71±0.27×10⁻⁷M，Vmax 15.8±1.6皮摩尔/10⁸个血小板⁻¹4分钟⁻¹），而敌草快和ANTU未能改变血小板对5-HT摄取的动力学。这些变化似乎需要一种能够产生氧自由基通量的肺毒物，并非由于残留毒物的存在、富含血小板血浆中内源性抑制剂的存在，或内源性5-HT的血小板含量变化所致。这项研究表明高氧和百草枯会影响血小板功能，并提示这种改变可能有助于肺微血管对这些药物所致损伤的病理生理反应。
