Stefano G B, Leung M K, Zhao X H, Scharrer B
Multidisciplinary Center for the Study of Aging, State University of New York/College at Old Westbury, NY 11568.
Proc Natl Acad Sci U S A. 1989 Jan;86(2):626-30. doi: 10.1073/pnas.86.2.626.
Evidence for the participation of opioid neuropeptides in immunoregulatory activities, especially cellular adherence and migration, has been obtained in representatives of two phyla of invertebrates, the mollusc Mytilus edulis and the insect Leucophaea maderae. The injection of a synthetic analog of [Met]enkephalin [( D-Ala2,Met5]enkephalinamide, DAMA; 10(-6) M) had a stimulatory, naloxone-reversible effect on the directed migration of immunocompetent hemocytes. Incubation of hemolymph in the presence of exogenous or endogenous opioid material significantly enhanced the adherence of hemocytes on albumin-coated slides as demonstrated by use of indirect Zeiss-Zonax reflectance computer analysis. Conversely, hemocyte adherence was markedly reduced by the addition of naloxone (10(-8) M) to the incubation medium, either alone or in combination with DAMA. The antagonistic effects of naloxone on the stimulatory activities of opioids indicate that, like those previously reported in mammals, they are receptor-mediated. The presence of an endogenous [Met]enkephalin-like material was demonstrated in cell-free hemolymph as well as sequestered hemocytes by use of high-pressure liquid chromatography and radioimmunoassay. These results demonstrate that the capacity of immunocytes to release and respond to opioid neuropeptide messengers is not restricted to mammalian organisms but was developed early in the course of evolution.
在两种无脊椎动物门的代表动物,即贻贝(软体动物)和马德拉蜚蠊(昆虫)中,已获得阿片类神经肽参与免疫调节活动,尤其是细胞黏附和迁移的证据。注射[甲硫氨酸]脑啡肽的合成类似物[(D - 丙氨酸2,甲硫氨酸5]脑啡肽酰胺,DAMA;10(-6)M)对免疫活性血细胞的定向迁移具有刺激作用,且该作用可被纳洛酮逆转。如通过蔡司 - 佐纳克斯间接反射计算机分析所示,在外源或内源性阿片类物质存在的情况下孵育血淋巴,可显著增强血细胞在白蛋白包被载玻片上的黏附。相反,单独或与DAMA联合向孵育培养基中添加纳洛酮(10(-8)M),可使血细胞黏附显著降低。纳洛酮对阿片类物质刺激活性的拮抗作用表明,与先前在哺乳动物中报道的情况一样,它们是受体介导的。通过高压液相色谱和放射免疫测定法,在无细胞血淋巴以及隔离的血细胞中证实了内源性[甲硫氨酸]脑啡肽样物质的存在。这些结果表明,免疫细胞释放和响应阿片类神经肽信使的能力并不局限于哺乳动物,而是在进化过程中很早就已形成。