title: Saturation of monoamine oxidase by intraneuronal noradrenaline accumulation.
abstract: After pretreatment of the rats with reserpine and pargyline (to inhibit vesicular uptake and MAO), after an additional in vitro treatment with pargyline, and in the presence of U-0521 (to inhibit COMT), the adrenergic nerve endings of vasa deferentia were loaded with 3H-(-)-noradrenaline by exposure to various concentrations of this amine. Subsequently, tissues were washed out with amine-free solution, and the neuronal efflux of tritium was analysed. During 180 min of wash-out the apparent rate constant for the efflux of tritium decreased with increasing tritium content of the tissue. Prolongation of the wash-out period to 305 min revealed that efflux curves for tritium from heavily loaded tissues became steeper after the 180th min of wash-out. This phenomenon is indicative of saturation (followed by desaturation) of a process that limits the efflux of tritium from heavily loaded tissues. Analysis of the radioactivity of the efflux revealed a characteristic efflux curve for DOPEG: the formation of DOPEG appears to be saturated when the 3H-(-)-noradrenaline content of the tissue is high, in order to become desaturated during prolonged wash-out. These results cannot distinguish between MAO and alcohol dehydrogenase as the saturable enzyme. The formation of the mainly deaminated metabolites (during 60 min of wash-out) was determined in lightly and in heavily loaded tissues. The ratio "formation of metabolites/3H-(-)-noradrenaline content" was lower in heavily than in lightly loaded tissues; the relative decline in DOPEG formation was not accompanied by a compensatory increase in the formation of DOMA.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008333:Mandelic Acids / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D009411:Nerve Endings / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects; D014649:Vas Deferens / Q000294:innervation
chemical_list: D008333:Mandelic Acids; D008734:Methoxyhydroxyphenylglycol; C000989:3,4-dihydroxymandelic acid; D012110:Reserpine; D010293:Pargyline; D008995:Monoamine Oxidase; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine