On the mechanism of the involvement of monoamine oxidase in catecholamine-stimulated prostaglandin biosynthesis in particulate fraction of rat brain homogenates: role of hydrogen peroxide.
The mechanism of involvement of monoamine oxidase (MAO) in catecholamine-stimulated prostaglandin (PG) biosynthesis was studied in the particulate fraction of rat brain homogenates. High concentrations of either noradrenaline (NA) or dopamine (DA) stimulated effectively PGF2 alpha formation. The same amount of 2-phenylethylamine (PEA) acted similarly, provided that it was administered together with a catecholamine analogue or metabolite possessing the 3,4-dihydroxyphenyl nucleus--3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3,4-dihydroxyphenylglycol (DOPEG), 3,4-dihydroxyphenylacetaldehyde (DOPAL), or alpha-methylnoradrenaline (alpha-met-NA)--or with SnCl2. In the absence of PEA, these compounds were ineffective with regard to stimulation of PGF2 alpha formation. Catalase, pargyline, or indomethacin abolished completely PGF2 alpha formation elicited either by catecholamines or by PEA plus a 3,4-dihydroxyphenyl compound or SnCl2. With regard to the stimulation of PGF2 alpha formation in the presence of alpha-met-NA, PEA could be replaced by H2O2 generated by the glucose oxidase(GOD)-glucose system. The effect of H2O2 was inhibited by indomethacin or catalase, but pargyline was ineffective. It is assumed that catecholamines play a dual role in the activation of PG biosynthesis in brain tissue. During the enzymatic decomposition of catecholamines MAO produces H2O2, which stimulates endoperoxide synthesis. Simultaneously, catecholamines as hydrogen donors promote the nonenzymatic transformation of endoperoxides into PGF2 alpha. The possible physiological importance of these findings is discussed.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D011460:Prostaglandins F / Q000096:biosynthesis*; D051381:Rats; D014001:Tin / Q000494:pharmacology; D017971:Tin Compounds
D010627:Phenethylamines; D011460:Prostaglandins F; D017971:Tin Compounds; C023599:stannous chloride; C029261:phenethylamine; D014001:Tin; D010293:Pargyline; D006861:Hydrogen Peroxide; D002374:Catalase; D008995:Monoamine Oxidase; D004298:Dopamine; C100006:prostaglandin F1; D009638:Norepinephrine; D007213:Indomethacin