Modulation of the production of reactive oxygen species by pre-activated neutrophils by aminoadamantane derivatives.
Aminoadamantane derivatives (AAD) such as amantadine or memantine have been used for the treatment of Morbus Parkinson and Morbus Alzheimer. In this communication, we report on the immunomodulatory activities of AAD. Luminol-dependent chemiluminescence of zymosan-, N-formylmethionylleucylphenylalanine(FMLP)- or experimental Ca2+-ionophore(A 231879)-preactivated polymorphonuclear leukocytes (PMN) was strongly enhanced by submicromolar concentrations of AAD and inhibited at higher concentrations than 0.1 mM. Light emission by phorbol-12-myristate-acetate(PMA)-preactivated cells was not further stimulated but inhibited by the elevated concentrations, just as with the other, above-mentioned activators. Ethylene formation from alpha-keto-methylthiobutyrate (KMB) as an indicator for production of OH.-type reactive oxygen species by the NADPH-oxidase ("respiratory burst") was augmented by AAD and completely inhibited by superoxide dismutase. In contrast, ethylene release from 1-amino-cyclopropyl-l-carboxylic acid (ACC) as relatively specific indicator for the myeloperoxidase reaction after degranulation was not influenced by AAD. As documented by several model reactions, AAD per se did not act as scavengers or quenchers of activated oxygen species such as superoxide, OH.-radical, hydrogen peroxide or hypochlorite. Altogether, these results suggest that submicromolar concentrations of AAD upregulate the respiratory burst, but apparently not the degranulation of prestimulated polymorphonuclear leukocytes. At higher concentrations of AAD, both respiratory burst and degranulation are inhibited, however. These effects can also be shown in complete blood samples.
Albrecht-Goepfert
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Technische Universität München, Lehrstuhl für Phytopathologie, (Labor F.Angewandte Biochemie), Freising, Germany.
Schempp
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Elstner
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D000547:Amantadine / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000598:Amino Acids, Cyclic; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005030:Ethylenes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008559:Memantine / Q000494:pharmacology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013552:Swine; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D000975:Antioxidants; D005030:Ethylenes; D010879:Piperazines; D017382:Reactive Oxygen Species; D000515:alpha 1-Antitrypsin; C023863:1-aminocyclopropane-1-carboxylic acid; C036216:ethylene; D000547:Amantadine; D009195:Peroxidase; D008559:Memantine; C007306:triethylenediamine