The renal handling of dopamine originating from <scp>l</scp>‐DOPA and γ‐glutamyl‐<scp>l</scp>‐DOPA

Pestana, Manuel; Soares‐da‐Silva, Patrício

doi:10.1111/j.1476-5381.1994.tb13088.x

Cited by 15 publications

(7 citation statements)

References 24 publications

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“…The outflow of dopamine and DOPAC in renal tissues loaded with L-DOPA (100IM) was found to decrease progressively with time ( Figure 1), but did not exhibit a monophasic decline, as evidenced by their upward concave shape when the levels of dopamine (from 0.84 ± 0.10 to 0.16 ± 0.03 nmol g' 10 min ') and DOPAC (0.80 ± 1.0 to 0.24 ± 0,02 nmol g-10 min') in the perifusate were logarithmically transformed and plotted against the time of perifusion (not shown, but see Pestana & Soares-da-Silva, 1994). Under control conditions, however, the decline of DOPAC outflow throughout the perifusion period did not follow that of dopamine; this is shown by the progressive increase of DOPAC/dopamine ratios in the perifusate (from 0.95 ± 0.07 to 1.77 ± 0.25, n = 8, Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Effect of type A and B monoamine oxidase selective inhibition by Ro 41–1049 and Ro 19–6327 on dopamine outflow in rat kidney slices

Pestana

Soares‐da‐Silva

1994

British J Pharmacology

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1 The influence of pargyline and of selective inhibitors of type A and B monoamine oxidase (MAO), Ro 41-1049 and Ro 19-6327 respectively, on the outflow of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA) was examined. Dopamine and DOPAC in the tissues and in the effluent were assayed by means of h.p.l.c. with electrochemical detection. 2 The levels of newly-formed dopamine and DOPAC in the perifusate decreased progressively with time. In control conditions, DOPAC/dopamine ratios in the perifusate were 3 to 5 fold those in the tissue and were found to increase progressively with time. The addition of pargyline (100 ItM), produced a marked decrease in the outflow levels of DOPAC (45 to 54% reduction) and significantly increased the levels of dopamine in the effluent (102 to 158% increase); DOPAC/dopamine ratios in the perifusate remained stable throughout the perifusion and were similar to those found in the tissues. The addition of the MAO-A inhibitor Ro 41-1049 to the perifusion fluid also significantly decreased DOPAC outflow (41% to 54% reduction) and increased dopamine outflow (19% to 80% increase). In the presence of Ro 41-1049 DOPAC/dopamine ratios in the perifusate were lower (P<0.01) than in controls; in contrast with the effect of pargyline, this ratio was found to increase (P < 0.01) throughout the perifusion period. Ro 19-6327 did not reduce the outflow of DOPAC, but significantly increased (by 40-60%) that of dopamine. In the presence of Ro 19-6237, the proportion of DOPAC to dopamine in the perifusate was similar to that of controls and significantly increased throughout the perifusion; however, this increase was less than that observed in the control group. 3 When benserazide (50 JAM) was added to the perifusion fluid, the levels of both dopamine and DOPAC in the effluent were similar to those observed in the absence of benserazide. However, in the presence of benserazide, DOPAC/dopamine ratios in the perifusate did not increase with time. In conditions of decarboxylase inhibition, the effects of pargyline, Ro 41-1049 and Ro 19-6327 on dopamine and DOPAC outflow were less pronounced than in experiments conducted in the absence of benserazide. 4 In conclusion, the results presented here show that the fraction of newly-formed dopamine which leaves the compartment where the synthesis has occurred is a constant source for deamination into DOPAC. The results provide evidence favouring the view that MAO-A is the main form of the enzyme involved in this process; however, the data described here suggest that dopamine would also have access to MAO-B.

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Section: Resultsmentioning

confidence: 99%

Effect of type A and B monoamine oxidase selective inhibition by Ro 41–1049 and Ro 19–6327 on dopamine outflow in rat kidney slices

Pestana

Soares‐da‐Silva

1994

British J Pharmacology

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“…The dopamine precursor l ‐dihydroxyphenylalanine (L‐DOPA) is filtered at the glomerulus and is taken up by the proximal tubule, where it is converted to dopamine by aromatic l ‐amino acid decarboxylase (L‐AADC) (13). The regulation of this non‐neuronal dopaminergic system depends mainly on the availability of L‐DOPA, on its decarboxylation into dopamine and on cell outward amine transfer mechanisms (13, 14). L‐DOPA uptake in renal epithelial cells is promoted through the sodium‐independent and pH‐sensitive L‐type AAT type 2 (LAT2), the activity of which might rate‐limit the synthesis of renal dopamine.…”

Section: Renal Dopaminergic Systemmentioning

confidence: 99%

“…As depicted in Fig. 1, renal dopamine is metabolized predominantly by catechol‐ O ‐methyl‐transferase (COMT) and monoamine oxidase (MAO) to 3,4‐dihydroxyphenylacetic acid (DOPAC), and to homovallinic acid (13, 14). The effects of dopamine, in mammals, are mediated by 5 dopamine receptor subtypes.…”

Section: Renal Dopaminergic Systemmentioning

confidence: 99%

Renal amino acid transport systems and essential hypertension

Pinto

Pinho²,

Soares-da-Silva³

2013

FASEB j.

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Several clinical and animal studies suggest that "blood pressure goes with the kidney," that is, a normotensive recipient of a kidney genetically programmed for hypertension will develop hypertension. Intrarenal dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport. The candidate transport systems for L-DOPA, the source for dopamine, include the sodium-dependent systems B(0), B(0,+), and y(+)L, and the sodium-independent systems L (LAT1 and LAT2) and b(0,+). Renal LAT2 is overexpressed in the prehypertensive spontaneously hypertensive rat (SHR), which might contribute to enhanced L-DOPA uptake in the proximal tubule and increased dopamine production, as an attempt to overcome the defect in D1 receptor function. On the other hand, it has been recently reported that impaired arginine transport contributes to low renal nitric oxide bioavailability observed in the SHR renal medulla. Here we review the importance of renal amino acid transporters in the kidney and highlight pathophysiological changes in the expression and regulation of these transporters in essential hypertension. The study of the regulation of renal amino acid transporters may help to define the underlying mechanisms predisposing individuals to an increased risk for development of hypertension.

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“…In a fifth group of rats, olive oil (0.5 ml kg-' day-', s. (Fernandes & Soares-da-Silva, 1992 Outflow ofdopamine The kinetic parameters of the outflow of dopamine and DOPAC in renal tissues of rats treated with CsA (n = 4) or olive oil (n = 4) for 14 days were determined as previously described (Pestana & Soares-da-Silva, 1994b). Briefly, on the 14th day of CsA administration, rats were given L-DOPA (30 mg kg-, i.p.)…”

Section: In Vitro Studiesmentioning

confidence: 99%

Assessment of renal dopaminergic system activity during cyclosporine A administration in the rat

Pestana

Vieira-Coelho²,

Pinto-do-Ó³

et al. 1995

British J Pharmacology

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1 Administration of cyclosporine A (CsA; 50 mg kg-' day-, s.c.) for 14 days produced an increase in both systolic (SBP) and diastolic (DBP) blood pressure by 60 and 25 mmHg, respectively. The urinary excretion of dopamine, DOPAC and HVA was reduced from day 5-6 of CsA administration onwards (dopamine from 19 to 46%, DOPAC from 16 to 48%; HVA from 18 to 42%). In vehicle-treated rats, the urinary excretion of dopamine and DOPAC increased (from 7 to 60%) from day 5 onwards; by contrast, the urinary excretion of HVA was reduced (from 27 to 60%) during the second week. 5 The accumulation of newly-formed dopamine and DOPAC in cortical tissues of rats treated with CsA for 14 days was three to four times higher than in controls. The outflow of both dopamine and DOPAC declined progressively with time and reflected the amine and amine metabolite tissue contents. No significant difference was observed between the DOPAC/dopamine ratios in the perifusate of renal tissues obtained from CsA-and vehicle-treated rats. In addition, no significant differences were observed in k values or in the slope of decline of both DA and DOPAC between experiments performed with CsA and vehicle-treated animals.6 The V, for the saturable component of L-3,4-dihydroxyphenylalanine (L-DOPA) uptake in renal tubules from rats treated with CsA was twice that of vehicle-treated animals. Km in CsA-and vehicletreated rats did not differ. 7 The decrease in the urinary excretion of sodium and an increase in blood pressure during CsA treatment was accompanied by a reduction in daily urinary excretion of dopamine. This appears to result from a reduction in the amount of L-DOPA made available to the kidney and does not involve changes in tubular AAAD, the availability of dopamine to leave the renal cells and dopamine metabolism. The enhanced ability of the renal tissues of CsA-treated animals to synthesize dopamine, when exogenous L-DOPA is provided, results from an enhanced activity of the uptake process of L-DOPA in renal tubular cells.

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The renal handling of dopamine originating from l‐DOPA and γ‐glutamyl‐l‐DOPA

Cited by 15 publications

References 24 publications

Effect of type A and B monoamine oxidase selective inhibition by Ro 41–1049 and Ro 19–6327 on dopamine outflow in rat kidney slices

Effect of type A and B monoamine oxidase selective inhibition by Ro 41–1049 and Ro 19–6327 on dopamine outflow in rat kidney slices

Renal amino acid transport systems and essential hypertension

Assessment of renal dopaminergic system activity during cyclosporine A administration in the rat

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