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)
Grohmann
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Henseling
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Cassis
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Trendelenburg
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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