Errors introduced by a tritium label in position 8 of catecholamines.
The neuronal and extraneuronal disposition of 3H-7,8- and 3H-7-labelled (-)-noradrenaline and dopamine was compared in in vitro studies. In agreement with earlier studies, the present results show that the presence of a tritium label in position 8 (i.e., on the alpha-carbon) has two consequences: a) the rate of deamination declines and b) part of the deamination results in the formation of an unlabelled aldehyde plus tritium water; tritium water is recovered from the OMDA-fraction of the column chromatographic procedure of Graefe et al. (1973). Whenever the deamination of a 3H-catecholamine is reduced (by tritium in position 8), the intraneuronal 3H-catecholamine concentration is increased. This increase, in turn, partly masks the decline in neuronal deamination (rat vas deferens). Irrespective of whether one determines the spontaneous efflux, the release of 3H-noradrenaline by nerve stimulation or the release of 3H-(-)-noradrenaline by the reserpine-like compound Ro 4-1284, the presence of tritium in position 8 distorts the results (experiments with rat vasa deferentia and/or rabbit aorta). In the extraneuronal system of the rat heart, two intracellular enzymes inactivate 3H-(-)-noradrenaline and 3H-dopamine: catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO). Any hindrance of deamination (by tritium in position 8, COMT intact) leads to a shift of the metabolism of the 3H-catecholamines from the exclusively deaminated to the exclusively O-methylated metabolites. No differences between 3H-7,8- and 3H-7-labelled catecholamines were found after inhibition of MAO and COMT (extraneuronal accumulation and rate constant for efflux from the extraneuronal compartment III of the rat heart).(ABSTRACT TRUNCATED AT 250 WORDS)
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Grohmann
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Henseling
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Cassis
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Trendelenburg
D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy- / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D003641:Deamination; D066298:In Vitro Techniques; D007553:Isotope Labeling; D008297:Male; D008333:Mandelic Acids / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D014649:Vas Deferens / Q000378:metabolism
D002395:Catecholamines; D008333:Mandelic Acids; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; C005975:3,4-dihydroxyphenylethanol; D012369:2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-; D008734:Methoxyhydroxyphenylglycol; C000989:3,4-dihydroxymandelic acid; D010626:Phenylethyl Alcohol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine