Singh S, Singh P P, Dhawan V C, Haq W, Mathur K B, Dutta G P, Srimal R C, Dhawan B N
Division of Microbiology, Central Drug Research Institute, Lucknow, India.
Immunopharmacology. 1994 May-Jun;27(3):245-51. doi: 10.1016/0162-3109(94)90020-5.
Methionine-enkephalin (ME) and its synthetic congener Tyr-D-Ala-Gly-Me-Phe-Gly-NH.C3H7-iso (82/205), in a concentration-dependent biphasic manner modulated the concanavalin A (Con A)-stimulated phagocytosis-promoting (PP)-activity elaboration in the culture supernatants of mouse splenocytes in vitro. Both these peptides at 1 x 10(-5) and 1 x 10(-6) M inhibited the production of PP activity; conversely, at 1 x 10(-7)-1 x 10(-9) M they augmented it. Peptide 82/205 was nearly 1.2-fold more inhibitory and approximately 1.8-fold more potent in augmenting the PP activity elaboration. The PP activity appeared to be due to lymphokines (LK) gamma interferon and interleukin-4 as the neutralizing concentrations of monoclonal antibodies against these LK significantly (p < 0.05) inhibited it. Cycloheximide (50.0 micrograms/ml) completely inhibited the production of LK indicating their de novo synthesis. The peptides appeared to exert their inhibitory and augmenting effects via delta- and mu-opioid receptors, respectively, as pretreatment of splenocytes with 100-fold higher (1 x 10(-3) M) concentration of naloxone was required to block their inhibitory effect; the augmenting effect was blocked by 1 x 10(-5) M only. None of the peptides or naloxone could directly stimulate the splenocytes for PP-LK elaboration.
甲硫氨酸脑啡肽（ME）及其合成类似物Tyr-D-Ala-Gly-Me-Phe-Gly-NH.C3H7-iso（82/205），以浓度依赖性双相方式，在体外调节小鼠脾细胞培养上清液中伴刀豆球蛋白A（Con A）刺激的促吞噬（PP）活性的产生。这两种肽在1×10⁻⁵和1×10⁻⁶ M时抑制PP活性的产生；相反，在1×10⁻⁷ - 1×10⁻⁹ M时它们增强了PP活性。肽82/205的抑制作用强约1.2倍，增强PP活性产生的效力约强1.8倍。PP活性似乎归因于淋巴因子（LK）γ干扰素和白细胞介素-4，因为针对这些LK的单克隆抗体的中和浓度显著（p < 0.05）抑制了它。放线菌酮（50.0微克/毫升）完全抑制了LK的产生，表明它们是从头合成的。这些肽似乎分别通过δ和μ阿片受体发挥其抑制和增强作用，因为需要用100倍更高（1×10⁻³ M）浓度的纳洛酮预处理脾细胞来阻断其抑制作用；增强作用仅被1×10⁻⁵ M阻断。这些肽或纳洛酮均不能直接刺激脾细胞产生PP-LK。
