Gruba Sarah M, Francis Danielle H, Meyer Audrey F, Spanolios Eleni, He Jiayi, Meyer Ben M, Kim Donghyuk, Xiong-Hang Kang, Haynes Christy L
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States.
ACS Meas Sci Au. 2022 Feb 16;2(1):4-13. doi: 10.1021/acsmeasuresciau.1c00012. Epub 2021 Aug 24.
Opioids are typically used for the treatment of pain related to disease or surgery. In the body, they enter the bloodstream and interact with a variety of immune and neurological cells that express the μ-, δ-, and κ-opioid receptors. One blood-borne cell-like body that is not well understood in the context of opioid interactions is the platelet. The platelet is a highly sensitive anucleate cell-like fragment responsible for maintaining hemostasis through shape change and the secretion of chemical messengers. This research characterizes platelet opioid receptors, how specific receptor agonists impact platelet exocytosis, and the role of the κ-and μ-receptors in platelet function. Platelets were found to express all three opioid receptors, but upon stimulation with their respective agonist no activation was detected. Furthermore, exposure to the opioid agonists did not impact traditional platelet secretion stimulated by thrombin, a natural platelet activator. In addition, data collected from knockout mice suggest that the opioid agonists may be interacting nonspecifically with platelets. Dark-field images revealed differences in activated platelet shape between the κ- and μ-knockout platelets and the control platelets. Finally, κ-knockout platelets showed variations in their ability to adhere and aggregate compared to control platelets. Overall, these data show that platelet function is not likely to be heavily affected by blood-borne opioids.
阿片类药物通常用于治疗与疾病或手术相关的疼痛。在体内，它们进入血液并与多种表达μ、δ和κ阿片受体的免疫和神经细胞相互作用。在阿片类药物相互作用的背景下，一种未被充分了解的血源细胞样体是血小板。血小板是一种高度敏感的无核细胞样碎片，负责通过形状变化和化学信使的分泌来维持止血。本研究对血小板阿片受体进行了表征，特定受体激动剂如何影响血小板胞吐作用，以及κ和μ受体在血小板功能中的作用。研究发现血小板表达所有三种阿片受体，但在用各自的激动剂刺激后未检测到激活。此外，暴露于阿片激动剂对由凝血酶（一种天然血小板激活剂）刺激的传统血小板分泌没有影响。此外，从基因敲除小鼠收集的数据表明，阿片激动剂可能与血小板发生非特异性相互作用。暗视野图像显示κ和μ基因敲除血小板与对照血小板在激活的血小板形状上存在差异。最后，与对照血小板相比，κ基因敲除血小板在粘附和聚集能力上表现出差异。总体而言，这些数据表明血小板功能不太可能受到血源阿片类药物的严重影响。
