Saurer Timothy B, Ijames Stephanie G, Lysle Donald T
Department of Psychology, Davie Hall, CB#3270, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA.
J Neuroimmunol. 2006 Aug;177(1-2):18-26. doi: 10.1016/j.jneuroim.2006.05.002.
Morphine suppresses a number of immune parameters, such as natural killer (NK) cell activity and lymphocyte proliferation, by acting through mu-opioid receptors in the central nervous system. Prior studies have implicated the sympathetic nervous system in mediating the immunomodulatory effects of acute morphine treatment. However, the peripheral mechanism whereby morphine inhibits NK cell activity is not fully understood. The aim of the present study was to investigate the role of the sympathetic transmitter neuropeptide Y (NPY) in mediating morphine-induced immune alterations. The results showed that administration of the selective NPY Y1 receptor antagonist BIBP3226 blocked morphine's effect on splenic NK activity but did not attenuate the suppression splenocyte proliferative responses to Con-A or LPS. Furthermore, intravenous NPY administration produced a dose-dependent inhibition of splenic NK activity but did not suppress lymphocyte proliferation. Recent studies from our laboratory have demonstrated that morphine modulates NK activity through a central mechanism that requires the activation of dopamine D1 receptors in the nucleus accumbens. Results from the present study showed that microinjection of the D1 receptor agonist SKF-38393 into the nucleus accumbens shell induced a suppression of NK activity that was reversed by BIBP3226. Collectively, these findings demonstrate that NPY Y1 receptors mediate morphine's suppressive effect on NK activity and further suggest that opioid-induced increases in nucleus accumbens D1 receptor activation inhibit splenic NK activity via NPY released from the sympathetic nervous system.
吗啡通过作用于中枢神经系统的μ-阿片受体，抑制多种免疫参数，如自然杀伤（NK）细胞活性和淋巴细胞增殖。先前的研究表明，交感神经系统参与介导急性吗啡治疗的免疫调节作用。然而，吗啡抑制NK细胞活性的外周机制尚未完全阐明。本研究的目的是探讨交感神经递质神经肽Y（NPY）在介导吗啡诱导的免疫改变中的作用。结果表明，给予选择性NPY Y1受体拮抗剂BIBP3226可阻断吗啡对脾脏NK活性的影响，但不会减弱对脾细胞对Con-A或LPS增殖反应的抑制作用。此外，静脉注射NPY可产生剂量依赖性的脾脏NK活性抑制，但不抑制淋巴细胞增殖。我们实验室最近的研究表明，吗啡通过一种需要伏隔核中多巴胺D1受体激活的中枢机制来调节NK活性。本研究结果表明，向伏隔核壳内微量注射D1受体激动剂SKF-38393可诱导NK活性的抑制，而BIBP3226可逆转这种抑制。总的来说，这些发现表明NPY Y1受体介导了吗啡对NK活性的抑制作用，并进一步表明阿片类药物诱导的伏隔核D1受体激活增加通过交感神经系统释放的NPY抑制脾脏NK活性。
