Singh Rajeev, Rai Umesh
Department of Zoology, University of Delhi, Delhi, India.
Peptides. 2009 Jun;30(6):1158-64. doi: 10.1016/j.peptides.2009.02.016. Epub 2009 Mar 13.
The immunoregulatory role of methionine-enkephalin (Met-enk) is well studied in mammals, but has not been explored in ectotherms despite the fact that this peptide is highly conserved in vertebrates. The present study demonstrates the diverse effects of Met-enk depending on its concentration and specific function of splenic phagocytes in the freshwater fish Channa punctatus. Although Met-enk increased both phagocytic as well as respiratory burst activity, the concentration-related response was opposite to each other. It had the maximum stimulatory effect on phagocytosis at 10(-9)M, while the same concentration was least effective in increasing superoxide production. Similarly, Met-enk at concentrations lower or higher than 10(-9)M was either ineffective or less effective in case of phagocytosis, while highly effective in stimulating superoxide production. On the other hand, concentration-independent inhibitory effect of Met-enk was observed in case of nitrite production. Nonetheless, Met-enk regulated all the functions of phagocyte through opioid receptors since non-specific opioid receptor antagonist naltrexone completely blocked the effect of Met-enk on phagocytosis, superoxide and nitrite production by splenic phagocytes of C. punctatus. Among selective opioid receptor antagonists, delta-opioid receptor antagonist naltrindole completely antagonized the effect of Met-enk on phagocytosis, superoxide and nitrite production, while mu- and kappa-opioid receptor antagonist, CTAP and norbinaltorphimine, respectively, were ineffective in influencing any of the functions. This suggests that Met-enk modulates splenic phagocyte functions in the fish C. punctatus via delta-opioid receptor. This is further substantiated by using highly selective delta-opioid receptor agonist, SNC80.
甲硫氨酸脑啡肽(Met-enk)的免疫调节作用在哺乳动物中已得到充分研究,但尽管这种肽在脊椎动物中高度保守,在变温动物中却尚未被探索。本研究证明了Met-enk在淡水鱼斑鳢中对脾吞噬细胞的不同影响,这取决于其浓度和特定功能。虽然Met-enk增加了吞噬作用以及呼吸爆发活性,但浓度相关的反应却彼此相反。它在10(-9)M时对吞噬作用具有最大刺激作用,而相同浓度在增加超氧化物产生方面效果最差。同样,浓度低于或高于10(-9)M的Met-enk在吞噬作用方面要么无效要么效果较差,而在刺激超氧化物产生方面则非常有效。另一方面,在亚硝酸盐产生的情况下观察到Met-enk具有浓度无关的抑制作用。尽管如此,Met-enk通过阿片受体调节吞噬细胞的所有功能,因为非特异性阿片受体拮抗剂纳曲酮完全阻断了Met-enk对斑鳢脾吞噬细胞吞噬作用、超氧化物和亚硝酸盐产生的影响。在选择性阿片受体拮抗剂中,δ-阿片受体拮抗剂纳曲吲哚完全拮抗了Met-enk对吞噬作用、超氧化物和亚硝酸盐产生的影响,而μ-和κ-阿片受体拮抗剂CTAP和去甲二氢吗啡酮分别在影响任何功能方面均无效。这表明Met-enk通过δ-阿片受体调节斑鳢的脾吞噬细胞功能。使用高度选择性的δ-阿片受体激动剂SNC80进一步证实了这一点。