Sources of Circulating Dopamine—A Personal View

Cuche, Jean-Louis

doi:10.1007/978-1-349-09503-2_1

Cited by 7 publications

(5 citation statements)

References 80 publications

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“…It has to be asked whether the t-Dopa dose was sufficient to reproduce the natriuretic effects of dopanline. Lehmann el nl (1990) report that an L-Dopa dose in healby volunteers, which increased urinary free dopamine excretion in a way similar to our results, was associated with an increase in the plasma dopamine level which has in turn been reported to induce natriuresis (Cuche, 1988). Was L-Dopa ingestion linked to alpha-adrenomimetic effects which could have blunted dopamine-induced natriuresis?…”

Section: Discussionsupporting

confidence: 80%

“…No medication was allowed in the week prior to the study and over the seven days between doses. On the days of the study and on the two preceding days, subjects agreed to refrain from eating banana, avocado and cereal-rich diets which contain either dopamine or tyrosine (Cuche, 1988). They also limited their intake of other fruits and vegetables since these are often rich in ascorbic acid or pyridoxine, which can modify dopamine and L-Dopa metabolism.…”

Section: Inclusion Of the Volitnteersmentioning

confidence: 99%

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Renal dopamine excretion in healthy volunteers after oral ingestion of l‐Dopa

Barthelmebs

Mbou

Stephan³

et al. 1993

Fundamemntal Clinical Pharma

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L-Dopa is converted to dopamine by aromatic-L-amino acid decarboxylase (AADC). In the kidney, proximal tubular epithelial cells are rich in AADC and urinary free dopamine excretion is a marker for endorenal extraneuronal dopamine synthesis. The urinary free dopamine excretion was analysed in a double-blind cross-over study after oral ingestion of L-Dopa or a placebo in five healthy volunteers. The drug ingestions were separated by one week's wash-out. Since in a preliminary study, two volunteers ingesting a single L-Dopa dose of 500 mg with breakfast experienced nausea, the five volunteers of the present study were given 300 mg L-Dopa (50 mg at 9 am with breakfast, 100 mg before lunch and 150 mg before dinner) without any adverse effects. L-Dopa induced an increase in 24-h urinary dopamine excretion (HPLC with electrochemical detection). Free urinary dopamine (1900 micrograms/24 h) accounted for 0.8% of the daily oral L-Dopa dose and represented 10% of total urinary dopamine excretion. L-Dopa treatment had no significant effect on mean ambulatory arterial blood pressure and heart rate measured from 9 am to 6 pm (Spacelabs) or on 24 h urinary water and sodium excretion.

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Section: Discussionsupporting

confidence: 80%

Section: Inclusion Of the Volitnteersmentioning

confidence: 99%

Renal dopamine excretion in healthy volunteers after oral ingestion of l‐Dopa

Barthelmebs

Mbou

Stephan³

et al. 1993

Fundamemntal Clinical Pharma

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“…This is a quantitatively important process as tubular epithelial cells have a high aromatic L-amino acid decarboxylase (AAAD) activity (Adam et al, 1986) and plasma levels of DOPA can attain concentrations up to 15 pmol ml 1 (Cuche, 1988). More recently, evidence obtained in studies performed under in vitro conditions have confirmed the view that renal tissues are endowed with an enormous capacity to synthesize dopamine from exogenous L-fl-3,4-dihydroxyphenylalanine (L-DOPA) and further showed that a substantial amount of newly-formed dopamine in renal tissues is deaminated to 3,4-dihydroxyphenylacetic acid (DOPAC) (Soares-da-Silva & Fernandes, 1990a).…”

Section: Introductionmentioning

confidence: 99%

Deamination of newly‐formed dopamine in rat renal tissues

Fernandes

Pestana

Soares-da-Silva

1991

British J Pharmacology

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1 The present study has examined the formation of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in slices of the rat renal cortex and the renal medulla loaded with exogenous L-fl-3,4-dihydroxyphenylalanine (L-DOPA). The effects of pargyline and of two selective inhibitors of monoamine oxidase (MAO) types A and B, respectively Ro 41-1049 and Ro 19-6327, on the deamination of newlysynthesized dopamine in kidney slices incubated with exogenous L-DOPA were also tested. The assay of L-DOPA, dopamine, noradrenaline and DOPAC was performed by means of h.p.l.c. with electrochemical detection. 2 Incubation of renal slices with exogenous L-DOPA resulted in a concentration-dependent accumulation of dopamine and DOPAC; the tissue levels of newly-formed dopamine and DOPAC in slices of the renal medulla were 6-8% of those in cortical slices. 3 Pargyline (0.1 mM) produced a marked decrease (84% reduction) in the formation of DOPAC in kidney slices loaded with 1.0mM L-DOPA; this effect was accompanied by a 17% increase in the accumulation of dopamine. Similar effects were obtained at higher concentrations of pargyline (0.5 and 1.0mM). At 5.0 and 10.0mm pargyline, a marked decrease (46 and 76% reduction) in the accumulation of newlyformed dopamine was observed. 4 The accumulation of dopamine and DOPAC was found to be time-dependent in experiments in which tissues were incubated with 5 and 1IOPM L-DOPA for 5, 10, 20 and 30min. Pargyline (0.1 mM) produced an increase in the accumulation of dopamine at all incubation periods and decreased the formation of DOPAC. 5Ro 41-1049 (50, 100 and 250 nM) was found to produce a concentration-dependent increase of newlyformed dopamine (16-66% increase) and reduced DOPAC formation (44-89% reduction). Ro 19-6327 (50, 100 and 250nM), was found not to affect the accumulation of newly-formed dopamine, but significantly reduced the formation of DOPAC. 6 It is concluded that deamination of newly-formed dopamine in kidney slices loaded with L-DOPA constitutes an important mechanism of amine inactivation. The results presented also suggest that most of the MAO, located inside the compartment where the synthesis of dopamine occurs, is of the A type.

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“…Because the dopamine produced in this area is in close proximity to epithelial cells which contain receptors for the amine, it has been hypothesized that the amine may act as a paracrine or autocrine substance (Vieira‐Coelho et al . 1997) Although the intestinal epithelium is endowed with one of the highest levels of AADC in the body and common foodstuffs are a major source of L ‐DOPA (Cuche 1988), the rate limiting step for the synthesis of dopamine in the intestinal epithelium is still a matter of debate.…”

mentioning

confidence: 99%

Regulation of apical transporter of L‐DOPA in human intestinal Caco‐2 cells

Fraga

Serrão

Soares-da-Silva

2002

Acta Physiologica Scandinavica

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The present study examined the nature of the apical inward L-3,4-dihydroxyphenylalanine (L-DOPA) transporter in human intestinal epithelial Caco-2 cells, and whether protein kinases modulate the activity of this transporter. The apical inward transfer of L-DOPA was promoted through an energy-dependent and sodium-insensitive transporter (Km=33 microM; Vmax=2932 pmol/mg protein/6 min). This transporter was insensitive to N-(methylamino)-isobutyric acid, but competitively inhibited by 2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BCH; IC50=83 microM). The organic cation inhibitor decynium 24 failed to affect the accumulation of L-DOPA, whereas the organic anion inhibitor 4,4'-diisothiocynatostilbene-2,2'-disulphonic acid (DIDS) competitively inhibited L-DOPA uptake (IC50=83 microM). However, the apical-to-basal and basal-to-apical transepithelial transport and the cell accumulation of [3H]-PAH was close to that of [14C]-sorbitol and insensitive to DIDS (300 microM). Modulators of protein kinase A (PKA) [cyclic adenosine monophosphate (cAMP), forskolin, H-89 and cholera toxin], protein kinase G (PKG) [cyclic guanosine monophosphate (GMP), zaprinast, LY 83583 and sodium nitroprusside] and protein kinase C (PKC) (phorbol 12,13-dibutirate and chelerythrine) failed to affect the accumulation of L-DOPA. The Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L-DOPA uptake (IC50s of 53 and 252 microM, respectively), but the rise of intracellular Ca2+ by A23187 (1 microM) and thapsigargin (1 microM) played no role on L-DOPA uptake. It is concluded that Caco-2 cells take up L-DOPA over the apical cell border through the sodium-independent and pH-sensitive L-type amino acid transporter.

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Sources of Circulating Dopamine—A Personal View

Cited by 7 publications

References 80 publications

Renal dopamine excretion in healthy volunteers after oral ingestion of l‐Dopa

Renal dopamine excretion in healthy volunteers after oral ingestion of l‐Dopa

Deamination of newly‐formed dopamine in rat renal tissues

Regulation of apical transporter of L‐DOPA in human intestinal Caco‐2 cells

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