Effect of catechol oestrogens on extraneuronal metabolism of noradrenaline by rabbit uterine endometrium and myometrium.
The effects of 2-hydroxy and 2-methoxy oestrogens on the extraneuronal O-methylation of 3H-(-)-noradrenaline were examined in progesterone-dominated, monoamine oxidase (MAO)-inhibited, rabbit uterine tissues in vitro. Both the corticosteroid-sensitive system in myometrium and the cocaine-sensitive system in endometrium were examined. In myometrial slices preincubated with nialamide to inhibit MAO and incubated with cocaine to inhibit neuronal uptake, 3H-normetanephrine (3H-NMN) formation was inhibited in the order of potency 2-hydroxy oestrone greater than or equal to 2-hydroxy oestradiol = 2-methoxy oestradiol greater than or equal to 2-methoxy oestrone. In myometrial slices not exposed to cocaine and nialamide, inhibition of 3H-NMN formation by both 2-hydroxy and 2-methoxy oestradiol did not affect the formation of deaminated metabolites of 3H-(-)-noradrenaline by the alternative metabolising pathway. In endometrial slices preincubated with nialamide to inhibit MAO, only 2-hydroxy oestrogens inhibited 3H-NMN formation, but they were one to two orders of magnitude less potent in this regard than in the myometrium. The uptake of 3H-(-)-noradrenaline by MAO- and COMT-inhibited myometrial slices was inhibited by 2-hydroxy and 2-methoxy oestrogens in the order of potency 2-methoxy oestradiol greater than or equal to 2-methoxy oestrone greater than or equal to 2-hydroxy oestrone greater than 2-hydroxy oestradiol. Uptake of 3H-(-)-noradrenaline by endometrial slices was not affected by either 2-hydroxy or 2-methoxy oestrogens.(ABSTRACT TRUNCATED AT 250 WORDS)
Kennedy
J A
JA
Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia.
D000077584:2-Methoxyestradiol; D000818:Animals; D065098:Catechol O-Methyltransferase Inhibitors; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000494:pharmacology*; D005260:Female; D006894:Hydroxyestrones / Q000494:pharmacology; D008745:Methylation; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D014316:Tritium
D065098:Catechol O-Methyltransferase Inhibitors; D002393:Estrogens, Catechol; D006894:Hydroxyestrones; D008996:Monoamine Oxidase Inhibitors; D014316:Tritium; D004958:Estradiol; D000077584:2-Methoxyestradiol; C001390:2-hydroxyestradiol; C003655:2-methoxyestrone; C024980:2-hydroxyestrone; D009638:Norepinephrine