Changes in cyclooxygenase activity and prostaglandin profiles during monoamine metabolism in rat brain homogenates.
The effect of different monoamine oxidase (MAO) substrates on the endogenous prostaglandin(PG) and thromboxane (TX) biosynthesis in rat brain homogenates was studied. In the absence of MAO substrates the following pattern of arachidonic acid metabolites was found: PGD2 greater than PGF2 alpha greater than TXB2 greater than PGE2 greater than or equal to 6ketoPGF1 alpha. Phenylethylamine(PEA) stimulated the cyclooxygenase activity 1.5-fold (expressed as the sum of the products formed), without altering the product profile. Tyrosine(Tyr) caused a twofold increase in cyclooxygenase activity and slightly modified the product composition (PGD2=PGF2 alpha greater than PGE2 greater than TXB2 greater than 6ketoPGF1 alpha). In the presence of noradrenaline(NA) there was a threefold stimulation of cyclooxygenase activity. The increase of PGF2 alpha was more pronounced than that of the other metabolites (PGF2 alpha greater than PGD2 greater than TXB2 greater than PGE2 greater than 6ketoPGF1 alpha). alpha-Methylnoradrenaline(alpha metNA ) (not a substrate for MAO but bearing the catechol group) altered the PG pattern in the same way as NA, but without enhancing the cyclooxygenase activity. PEA or Tyr when administered together with alpha metNA produced a NA-like effect both on the cyclooxygenase activity and on the product profile. The increase in cyclooxygenase activity was abolished by pargyline or by catalase, independently of the activator system used. The results support the hypothesis that NA-stimulation of brain PG (and TX) formation is mediated by H2O2 formed during the degradation of the amine via MAO. The role of the catechol group in protection of the cyclooxygenase against inactivation and in the changes of product composition, as well as the possible significance of the coupling between arachidonate and monoamine metabolism is discussed.
D000588:Amines / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008771:Nordefrin / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000494:pharmacology
D000588:Amines; D010627:Phenethylamines; D011453:Prostaglandins; D014443:Tyrosine; D011451:Prostaglandin-Endoperoxide Synthases; D008995:Monoamine Oxidase; D008771:Nordefrin; D009638:Norepinephrine