Oxygen dependency of monoamine oxidase activity in the intact lung.
Hydrogen peroxide generated by monoamine oxidase (MAO)-mediated deamination of biogenic amines has been implicated in cell signaling and oxidative injury. Because the pulmonary endothelium is a site of metabolism of monoamines present in the venous return, this brings into question a role for MAO in hyperoxic lung injury. The objective of this study was to evaluate the O(2) dependency of the MAO reaction in the lung. To this end, we measured the pulmonary venous effluent concentrations of the MAO substrate [(14)C]phenylethylamine and its metabolite [(14)C]phenylacetic acid after the bolus injection of either phenylethylamine or phenylacetic acid into the pulmonary artery of perfused rabbit lungs over a range of PO(2) values from 16 to 518 Torr. The apparent Michaelis constant for O(2) was approximately 18 microM, which is more than an order of magnitude less that measured for purified MAO. The results suggest a minimal influence of high O(2) on MAO activity in the normal lung and demonstrate the importance of measuring reaction kinetics in the intact organ.
Audi
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SH
Department of Biomedical Engineering, Marquette University, Milwaukee 53201-1881, USA. audis@marquette.edu
Dawson
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CA
Ahlf
S B
SB
Roerig
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DL
D000818:Animals; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology*; D008954:Models, Biological; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D010627:Phenethylamines / Q000493:pharmacokinetics; D010648:Phenylacetates / Q000493:pharmacokinetics; D011651:Pulmonary Artery / Q000502:physiology; D011817:Rabbits; D012663:Semicarbazides / Q000494:pharmacology
D002250:Carbon Radioisotopes; D002273:Carcinogens; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D010648:Phenylacetates; D012663:Semicarbazides; C010059:carbamylhydrazine; D010293:Pargyline; D008995:Monoamine Oxidase; C025136:phenylacetic acid; D010100:Oxygen