Haberstock H, Marotti T, Banfic H
Rudjer Boskovic Institute, Department of Experimental Biology and Medicine, Zagreb, Croatia.
Neuropeptides. 1996 Apr;30(2):193-201. doi: 10.1016/s0143-4179(96)90087-6.
The present study explored the involvement of signal transduction system(s) in Met-enkephalin (MENK) modulated superoxide anion (O2-) release from human neutrophils. This opioid pentapeptide stimulated the O2- release in all samples if present at 10(-8) M concentration while in lower concentrations the stimulatory concentration was donor-dependent. The most abundant product of MENK degradation, Tyr-Gly-Gly (TGG), suppressed O2- release over a wide range of concentrations (10(-12)-10(-8) M). MENK induced O2- release was associated with a dose-dependent increase of diacylglycerol (DAG) concentration and protein-kinase C (PKC) translocation to the neutrophil membranes, with an increase of cytosolic Ca++, and could be abolished by H7, a PKC inhibitor. On the contrary, the suppressive effect of TGG was not associated with alteration of DAG concentration in neutrophil membranes. Superoxide anion release induced by low concentrations of MENK (10(12)-10(-10) M), could be blocked by NDGA, an inhibitor of the lipoxygenase pathway. We concluded that MENK-induced O2- release results mainly due to DAG/PKC pathway activation, although other secondary messengers might be involved.
本研究探讨了信号转导系统在甲硫氨酸脑啡肽（MENK）调节人中性粒细胞超氧阴离子（O2-）释放中的作用。如果该阿片类五肽以10（-8）M的浓度存在，则会刺激所有样本中的O2-释放，而在较低浓度下，刺激浓度则取决于供体。MENK降解的最丰富产物，酪氨酸-甘氨酸-甘氨酸（TGG），在很宽的浓度范围（10（-12）-10（-8）M）内抑制O2-释放。MENK诱导的O2-释放与二酰基甘油（DAG）浓度的剂量依赖性增加以及蛋白激酶C（PKC）向中性粒细胞膜的转位有关，伴随着胞质Ca++的增加，并且可以被PKC抑制剂H7消除。相反，TGG的抑制作用与中性粒细胞膜中DAG浓度的改变无关。低浓度MENK（10（-12）-10（-10）M）诱导的超氧阴离子释放可以被脂氧合酶途径的抑制剂NDGA阻断。我们得出结论，MENK诱导的O2-释放主要是由于DAG/PKC途径的激活，尽管可能涉及其他第二信使。
