Extraneuronal uptake and O-methylation of 3H-adrenaline in the rabbit aorta.
The influence of uptake2 inhibitors on the O-methylation and accumulation of 3H-adrenaline by the isolated rabbit aorta was studied. Strips were incubated with 0.05 mumol/l 3H-(-)-adrenaline during 15 min. Monoamine oxidase and uptake1 were inhibited and the 3H-adrenaline present in the tissue was measured as well as the metabolites found in the tissue and in the incubation fluid. In another series of experiments, monoamine oxidase, uptake1 and catechol-O-methyl transferase (COMT) were inhibited, and tritium accumulation was measured in the tissue. When COMT was inhibited, inhibitors of uptake2 produced a maximal reduction of 3H-adrenaline accumulation that did not exceed 50%. When COMT was intact, inhibitors of uptake2 diminished total 3H-removal and, more markedly, O-methylation and concomitantly increased the tissue content of 3H-adrenaline. Mineralocorticoids (corticosterone and deoxycorticosterone acetate) inhibited 3H-adrenaline uptake (when COMT was inhibited) and 3H-metanephrine formation (when COMT was functional) as effectively as did sexual steroids (17-beta-oestradiol, progesterone and testosterone); hydrocortisone (hemisuccinate or phosphate) had no effect (for concentrations up to 120 mumol/l). At the end of the incubation some strips were washed out with amine-free solution. Compartmental analysis of the efflux showed that the amine had distributed into three extraneuronal compartments (compartment I, II and III, with half times of 0.4, 4 and 15 min, respectively). Corticosterone (120 mumol/l) decreased the amount of 3H-adrenaline in compartment III and simultaneously increased the amount of the amine in compartment I (extracellular space).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
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Martel
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Azevedo
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Osswald
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism* / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D008745:Methylation / Q000187:drug effects; D008996:Monoamine Oxidase Inhibitors; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology / Q000502:physiology; D010293:Pargyline / Q000494:pharmacology; D011817:Rabbits
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D008996:Monoamine Oxidase Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D010293:Pargyline; D003891:Desipramine; C057726:OR486; D004837:Epinephrine