Rhoads D L, Wei L X, Lin E T, Rezvani A, Way E L
Department of Pharmacology, School of Medicine and Drug Studies Unit, School of Pharmacy, University of California, San Francisco 94143.
NIDA Res Monogr. 1986;75:121-4.
In previous studies from this laboratory, it was noted that opioids in vitro reduced human red blood cell deformability. The effect was found to be dose-dependent, naloxone reversible and preferentially selective kappa ligands exhibited the highest potency. To extend these findings studies were carried out using rat erythrocytes. The time required for erythrocytes to pass through a 5.0 um pore membrane was determined and used as an index of deformability. Opioids added in vitro produced inhibition of deformability in a dose-dependent, naloxone reversible manner. Injecting naive animals with morphine or nalbuphine also produced dose related reductions in red cell deformability. The degree of inhibition produced by nalbuphine correlated well with its plasma concentrations as measured by high performance liquid chromatography (HPLC). Chronic morphine treatment by pellet implantation resulted in the development of tolerance as evidenced by a loss in the ability of morphine in vitro to inhibit red cell deformability. Addition of naloxone resulted in a decrease in filtration time. Thus, the data confirm and extend previous findings on human red blood cells. In as much as previous data from this laboratory demonstrated that opioids inhibit calcium flux from erythrocytes by inhibiting calcium-ATPase and calcium efflux is necessary for normal deformability, it is concluded that opioids act to reduce red cell deformability by inhibition of the calcium pump.
在本实验室之前的研究中，注意到阿片类药物在体外会降低人类红细胞的变形能力。发现该作用具有剂量依赖性，纳洛酮可逆转，且优先选择性κ配体表现出最高效力。为扩展这些发现，使用大鼠红细胞进行了研究。测定红细胞通过5.0微米孔径膜所需的时间，并将其用作变形能力的指标。体外添加阿片类药物会以剂量依赖性、纳洛酮可逆转的方式抑制变形能力。给未用药的动物注射吗啡或纳布啡也会导致红细胞变形能力出现剂量相关的降低。纳布啡产生的抑制程度与其通过高效液相色谱法（HPLC）测得的血浆浓度密切相关。通过植入药丸进行慢性吗啡治疗导致耐受性的产生，这表现为吗啡在体外抑制红细胞变形能力的能力丧失。添加纳洛酮会导致过滤时间缩短。因此，这些数据证实并扩展了先前关于人类红细胞的发现。鉴于本实验室之前的数据表明阿片类药物通过抑制钙 - ATP酶来抑制红细胞的钙通量，且钙外流对于正常变形能力是必需的，得出的结论是阿片类药物通过抑制钙泵来降低红细胞变形能力。
