Modification of the activity of mitochondrial monoamine oxidases in vitro and in vivo.
Treatment of bovine brain mitochondrial membranes with iproniazid (Ip) (1 mM, 15 min) inhibited monoamine oxidase (MAO) activity (substrates: 5-hydroxytryptamine, tyramine, dopamine) and significantly (about 7-fold) increased histamine deaminating activity (HDA). A selective inhibitor of MAO-A clorgyline (contrary to deprenyl) prevented the increase in HDA. Ip (200 mg/kg; within 10-16 h after parenteral administration) markedly (about 6-fold) increased the level of the HDA) in brain mitochondria of mice and guinea pigs. At the same time, a decrease in content of histamine (Hi) and increase in content of 5-hydroxytryptamine was noted in the brains of mice. In anesthetized and non-anesthetized guinea pigs Ip decreased (or prevented) the bronchoconstriction and toxic effects caused by Hi. The antihistamine effects of Ip are apparently due to its being able to induce reversible qualitative alteration (transformation) of the catalytic activity of the membrane-bound MAO of type A, which acquires as a result of this transformation potent HDA.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D004298:Dopamine / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007490:Iproniazid / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D014439:Tyramine / Q000378:metabolism
D006633:Histamine Antagonists; D012701:Serotonin; D006632:Histamine; D007490:Iproniazid; D008995:Monoamine Oxidase; D004298:Dopamine; D014439:Tyramine