The renal handling of dopamine originating from L-dopa and gamma-glutamyl-L-dopa. 1994

M Pestana, and P Soares-da-Silva
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.

1. The formation and outflow of dopamine and its deaminated metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) was studied in cortical fragments of the rat kidney loaded with L-beta-3,4-dihydroxyphenylalanine (L-dopa) or gamma-glutamyl-L-dopa (GluDOPA). Dopamine and DOPAC in the tissues and in the effluent were assayed by means of h.p.l.c. with electrochemical detection. 2. In rats given 30 mg kg-1 L-dopa, tissue and outflow levels of both dopamine and DOPAC were 3 fold those observed with a lower dose of L-dopa (10 mg kg-1). In rats given GluDOPA (16.7 mg kg-1) levels of dopamine in renal tissues and in perifusate samples were found to be higher than those obtained with an equimolar dose of L-dopa (10 mg kg-1); however, no significant difference was observed for DOPAC. The outflow of both dopamine and DOPAC in kidney slices of rats injected with L-dopa (10 and 30 mg kg-1) or GluDOPA (16.7 mg kg-1) was found to decline monophasically with similar slopes of decline. The rate constants of loss (k, min-1) of DOPAC (10 mg kg-1 L-DOPA, k = 0.0070; 30 mg kg-1 L-DOPA, k = 0.0087; 16.7 mg kg-1 GluDOPA, k = 0.0080) were 2 to 3 fold those of dopamine (10 mg kg-1 L-dopa, k = 0.0027; 30 mg kg-1 L-DOPA, k = 0.0034; 16.7 mg kg-1 GluDOPA, k = 0.0030). With both precursors the DOPAC/dopamine ratio in perifusate samples were 2.0 fold those in the tissues. 3. Tissue and outflow levels of dopamine after incubation of renal tissues with L-DOPA, 50 and 100 MicroM were found to be lower than those observed with GluDOPA (50 and 100 MicroM). DOPAC/dopamine ratios in tissues and perifusate samples of experiments performed with L-DOPA were significantly higher(P<0.01) than those observed with GluDOPA. The outflow of both dopamine and DOPAC in renal slices incubated with L-DOPA (50 and 100 MicroM) were found to decline with time, but presented a biphasic shape. DOPAC/dopamine ratios in perifusate samples were 3 fold that in the tissues with both precursors.4. In conclusion, the present results show that both L-DOPA and GluDOPA give origin to substantial amounts of dopamine and the newly-formed amine undergoes considerable deamination to DOPAC.However, dopamine originating from GluDOPA was less deaminated than that resulting from L-DOPA;it appears that this different behaviour may concern aspects related to the formation of the amine and also those related to its deamination and disposition, namely the processes involved in the access of newly-formed dopamine to MAO.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007980 Levodopa The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. L-Dopa,3-Hydroxy-L-tyrosine,Dopaflex,Dopar,L-3,4-Dihydroxyphenylalanine,Larodopa,Levopa,3 Hydroxy L tyrosine,L 3,4 Dihydroxyphenylalanine,L Dopa
D008297 Male Males
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004295 Dihydroxyphenylalanine A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific. Dopa,3,4-Dihydroxyphenylalanine,3-Hydroxy-DL-tyrosine,Dihydroxyphenylalanine Hydrochloride, (2:1),beta-Hydroxytyrosine,3 Hydroxy DL tyrosine,3,4 Dihydroxyphenylalanine,beta Hydroxytyrosine
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004563 Electrochemistry The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes. Electrochemistries
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015102 3,4-Dihydroxyphenylacetic Acid A deaminated metabolite of LEVODOPA. DOPAC,Homoprotocatechuic Acid,3,4-Dihydroxyphenylacetic Acid, Monosodium Salt,3,4 Dihydroxyphenylacetic Acid
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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