Outflow of dopamine and noradrenaline originating from L-dopa and L-threo-DOPS in rat renal tissues.
1. The present study has examined the formation and outflow of newly-formed dopamine (DA) and noradrenaline (NA) in slices of the renal cortex of rats given L-beta-3,4-dihydroxyphenylalanine (L-DOPA) (10, 30 or 100 mg/kg i.p.) and L-threo-3-(3,4-dihydroxyphenyl)serine (L-DOPS) (10, 30 or 100 mg/kg i.p.), respectively. The outflow of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylglycol (DOPEG), the deaminated metabolites of DA and NA, respectively, was also measured. 2. The accumulation of both newly-formed DA and DOPAC in renal tissues after the administration of L-DOPA was found to be dose dependent; after 30 or 100 mg/kg L-DOPA, the levels of both DA and DOPAC were, respectively, 3- and 20-fold those observed after the administration of 10 mg/kg L-DOPA. The outflow of DA and DOPAC in kidney slices of rats treated with L-DOPA was found to progressively decline with time and reflected the DA and DOPAC tissue contents. The rate constant (k) for DOPAC efflux (k = 0.0097) was higher (P < 0.01) than that for DA efflux (k = 0.0033) and did not depend on the dose of L-DOPA. DOPAC/DA perifusate ratios were 2-fold those occurring in the tissues. 3. The levels of NA in renal tissues of rats given 30 and 100 mg/kg L-DOPS were, respectively, 3- and 6-fold those observed after the administration of 10 mg/kg L-DOPS. The administration of L-DOPS was also found to be accompanied by the accumulation in renal tissues of DOPEG; this was, however, not dose dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
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Pestana
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Soares-Da-Silva
D000818:Animals; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015103:Droxidopa / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000502:physiology; D009638:Norepinephrine / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007980:Levodopa; D008995:Monoamine Oxidase; D015103:Droxidopa; D004298:Dopamine; D009638:Norepinephrine