Dopamine and adrenaline, but not isoprenaline, are substrates for uptake and metabolism in isolated perfused lungs of rats.
The uptake and subsequent metabolism by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) of dopamine, adrenaline, isoprenaline and noradrenaline in isolated perfused lungs of rats has been examined. In lung preparations in which COMT and MAO were inhibited, the uptake of 3H-labelled dopamine, (-)-adrenaline and (-)-noradrenaline, but not (+/-)-isoprenaline, was reduced by cocaine (10 or 100 mumol/l). The rank order of the Km values of the amines that were substrates for uptake in the lungs were: dopamine (0.246 mumol/l) less than noradrenaline (0.967 mumol/l) less than adrenaline (3.32 mumol/l). These results are consistent with transport of catecholamines in rat lungs by Uptake1. In lung preparations with COMT and MAO intact, dopamine and noradrenaline were removed from the circulation (50% and 32%, respectively) and mainly metabolized. There was very little (3.0%) removal of isoprenaline by the lungs and adrenaline was not included in this part of the study. In lung preparations in which only MAO was inhibited, the rank order of COMT activity for O-methylation of the amines was dopamine much much greater than noradrenaline greater than or equal to adrenaline (kCOMT values: 4.98 min-1, 0.357 min-1 and 0.234 min-1, respectively). If dopamine or adrenaline are perfused through the pulmonary circulation in isolated lungs of the rat, they are taken up and then metabolized by COMT and MAO, as also occurs for noradrenaline. Isoprenaline is not a substrate for uptake in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
Bryan-Lluka
L J
LJ
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
O'Donnell
S R
SR
D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004837:Epinephrine / Q000032:analysis / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000032:analysis / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D014316:Tritium; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D007545:Isoproterenol; D004298:Dopamine; D004837:Epinephrine