Inhibition of redox cycling of methoxatin (PQQ), and of superoxide release by phagocytic white cells.
The iodonium compounds diphenyleneiodonium and diphenyliodonium, and the amine compounds, 4,5-dimethyl phenylene diamine, N,N-dimethyl 1,4-phenylene diamine, 1,2-diamino-4,5-methyleneoxybenzene, and aminomalononitrile inhibit methoxatin's (PQQ's) redox activity in vitro, that is, the methoxatin-coupled oxidation of glycine and reduction of nitroblue tetrazolium to formazan. The compounds mentioned above also inhibit phorbol myristate acetate (PMA) stimulated superoxide release by phagocytic white cells--determined mainly as the superoxide dismutase sensitive reduction of ferricytochrome C. Related compounds, 3,4-diaminopyridine and 4-dimethylamino-benzylamine, did not inhibit redox activity of PQQ in vitro, nor did they inhibit PMA stimulated superoxide production in monocytes or neutrophils. Thus, there is a correlation between an agent's ability to inhibit PQQ redox cycling and its ability to inhibit superoxide release by phagocytes. The findings are a further indication that PQQ is involved in the respiratory burst of phagocytic cells.
Bishop
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A
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Paz
M A
MA
Gallop
P M
PM
Karnovsky
M L
ML
D000588:Amines / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D003067:Coenzymes / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D045542:PQQ Cofactor; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism*; D015363:Quinolones / Q000378:metabolism*; D016897:Respiratory Burst; D013481:Superoxides / Q000378:metabolism*
D000588:Amines; D001713:Biphenyl Compounds; D003067:Coenzymes; D005609:Free Radicals; D009861:Onium Compounds; D015363:Quinolones; C031291:diphenyliodonium; D013481:Superoxides; C007517:diphenyleneiodonium; D045542:PQQ Cofactor