Neutrophil signal transduction in Met-enkephalin modulated superoxide anion release.
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.
Haberstock
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H
Rudjer Boskovic Institute, Department of Experimental Biology and Medicine, Zagreb, Croatia.
Marotti
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T
Banfic
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H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000838:Anions; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000097:blood; D047428:Protein Kinase Inhibitors; D015398:Signal Transduction / Q000502:physiology*; D013481:Superoxides / Q000097:blood*
D000838:Anions; D016859:Lipoxygenase Inhibitors; D047428:Protein Kinase Inhibitors; D013481:Superoxides; D004744:Enkephalin, Methionine; D009637:Masoprocol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C