RESUMEN
AIMS: The interplay between natriuretic dopamine and antinatriuretic angiotensin II represents an important mechanism for the regulation of renal sodium and water excretion. Monoamine oxidase is the main metabolizing pathway for dopamine in the renal cortex. In this study, we have analysed the effect of low sodium feeding and AT1 receptor blockade on renal dopamine metabolism by monoamine oxidase. METHODS: Four groups of rats were studied: 1, normal salt diet (NS); 2, low salt diet (LS); 3, NS receiving Losartan (Los, specific AT1 receptor antagonist, 20 mg kg(-1) bwt day(-1), NS + Los); 4, LS receiving Los (LS + Los). RESULTS: Urinary dopamine excretion was lower in LS than in NS rats (543 +/- 32 vs. 680 +/- 34 ng day(-1) 100 g(-1) bwt, P < 0.05). When treated with Los, DOPAC excretion and urinary DOPAC/dopamine ratio fell significantly in the LS + Los group as compared with the LS group (1199 +/- 328 vs. 3081 +/- 681 ng day(-1) 100 g(-1) bwt and 1.90 +/- 0.5 vs. 5.7 +/- 1.2, respectively, both P < 0.02). Losartan increased hydroelectrolyte excretion in the LS group. No changes were found in the NS + Los group. Aromatic L-amino acid decarboxylase activity in cortex was similar in NS and LS rats. Instead, monoamine oxidase activity was higher in cortical homogenates from LS rats (in nmol mg tissue(-1) h(-1): NS 7.66 +/- 0.52; LS 9.82 +/- 0.59, P < 0.05) and this difference was abolished in LS + Los rats (7.34 +/- 0.49 nmol mg tissue(-1) h(-1), P < 0.01, vs. LS). CONCLUSIONS: We have concluded that low levels of dopamine in the urine of LS rats are because of an increase in the activity of renal monoamine oxidase and that angiotensin II mediates this increase through stimulation of AT1 receptors.
Asunto(s)
Angiotensina II/metabolismo , Dieta Hiposódica/métodos , Riñón/enzimología , Monoaminooxidasa/metabolismo , Ácido 3,4-Dihidroxifenilacético/orina , Aldosterona/sangre , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Presión Sanguínea/fisiología , Dopamina/orina , Tasa de Filtración Glomerular/fisiología , Losartán/farmacología , Masculino , Ratas , Ratas Wistar , Sodio/orinaRESUMEN
BACKGROUND/AIMS: This study determined alterations in renal dopamine production in streptozotocin-treated rats and explored the mechanisms underlying this alteration. METHODS: Streptozotocin (65 mg/kg) or vehicle was administered to 3-month-old male Wistar rats. Treated animals had hyperglycemia, glycosuria and increased diuresis, natriuresis and excretion of L-dopa. Urinary dopamine and dihydroxyphenylacetic acid were similar to those in control animals. The production of dopamine by renal cortex slices from treated rats was significantly less than that from control animals. The addition of glucose (8.4-18.4 mM) to the incubation medium decreased about 40% the uptake of L-dopa by isolated proximal tubular cells. Scatchard analysis of the saturation curves obtained in this condition showed a decrease in the V(max) without changes in the K(m). RESULTS: Our results confirm previous studies suggesting a renal dopaminergic deficiency in insulin-dependent diabetes and provide evidence strongly suggesting that a decrease in the number of tubular L-dopa transport sites is the underlying defect of this deficiency. CONCLUSION: These results highlight the role of the uptake of dopa as an important modulator of renal dopamine synthesis.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Túbulos Renales Proximales/metabolismo , Levodopa/farmacocinética , Ácido 3,4-Dihidroxifenilacético/orina , Animales , Transporte Biológico , Dopamina/deficiencia , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Glucosa/farmacología , Técnicas In Vitro , Riñón/metabolismo , Levodopa/farmacología , Levodopa/orina , Masculino , Concentración Osmolar , Ratas , Ratas WistarRESUMEN
This study determined the effects of thyroid hormone on the renal dopaminergic system. Surgical thyroidectomy (Tx) and treatment with 2-thiouracil (Thio) decreased renal cortex Na+/K+ ATPase activity and urinary volume. Tx also decreased urinary Na+ and urinary L-DOPA without changing urinary excretion of Dopamine (DA). Thio treatment decreased slightly urinary L-DOPA and Na+, but increased urinary excretion of DA. In both models of thyroid hormone deficiency, the ratio urinary DA/DOPA increased. Changes after Thio treatment were reversed after one month of drug withdrawal. Treatment with T3 via osmotic minipump increased Na+/K+ ATPase activity and urinary L-DOPA, did not change urinary DA, and increased the ratio DA/DOPA. To further analyze the effects of thyroid hormone deficiency, we administered selective DA1 (SCH-23390), DA2 (Sulpiride), and a non selective (Haloperidol) DA receptor antagonists to Thio treated and control animals. The DA1 antagonist decreased diuresis, natriuresis and urinary L-DOPA in control, but had no effect in Thio treated rats. Sulpiride had no effect in either group. The combination of SCH-23390 plus Sulpiride decreased urinary L-DOPA and urinary volume only in Thio treated animals. Haloperidol decreased urinary volume in Thio treated animals, but had no effect in controls. Our findings suggest that renal DA synthesis is to some extent dependent on thyroid hormone levels, and that the response of DA receptors is altered by thyroid hormone deficiency, indicating a role of this hormone in the regulation of the renal dopaminergic system.
Asunto(s)
Dopamina/fisiología , Riñón/efectos de los fármacos , Hormonas Tiroideas/farmacología , Ácido 3,4-Dihidroxifenilacético/metabolismo , Ácido 3,4-Dihidroxifenilacético/orina , Animales , Antitiroideos/farmacología , Benzazepinas/farmacología , Catecoles/metabolismo , Dihidroxifenilalanina/metabolismo , Dihidroxifenilalanina/orina , Dopamina/metabolismo , Antagonistas de Dopamina/farmacología , Haloperidol/farmacología , Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Masculino , Ratas , Receptores de Dopamina D1/antagonistas & inhibidores , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Tiouracilo/farmacología , Hormonas Tiroideas/sangre , TiroidectomíaRESUMEN
This study assessed the role of adrenergic receptors on the regulation of the uptake of L-dopa and the production of dopamine by renal tubular cells. Scatchard analysis showed two L-dopa uptake sites with different affinities (K(m) 0.316 vs 1.53 microM). L-Dopa uptake was decreased by the nonselective adrenergic agonists epinephrine or norepinephrine (40%), by the beta-selective agonist isoproterenol or the beta(2)-selective agonist terbutaline (60%), but not by alpha-selective agonists (all 1 microM). The effect of norepinephrine, isoproterenol, or terbutaline was unaffected by addition of the beta(1)-antagonist atenolol, abolished by ICI-118, 551, a beta(2)-antagonist (both 0.1 microM), and mimicked by the addition of dibutyryl-cAMP (1 microM). Preincubation with terbutaline decreased the number of high-affinity uptake sites (V(max) = 1.10 +/- 0.3 vs. 0.5 +/- 0.1 pmol. mg protein(-1). min(-1)) without changing their affinity. Norepinephrine or terbutaline decreased dopamine production by isolated cells, and this effect was abolished by ICI-118,551 (0.1 microM). In vivo administration of ICI-118,551 reduced the urinary excretion of L-dopa and increased the excretion of 3,4-dihydroxyphenylacetic acid without significant changes in plasma L-dopa concentrations. These results demonstrate that stimulation of beta(2)-adrenergic receptors decreases the number of high-affinity L-dopa uptake sites in isolated tubular cells resulting in a reduction of the uptake of L-dopa and the production of dopamine and provide evidence for the presence of this mechanism in the intact animal.
Asunto(s)
Dopamina/metabolismo , Túbulos Renales Proximales/metabolismo , Levodopa/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Ácido 3,4-Dihidroxifenilacético/orina , Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacología , Animales , Sitios de Unión , Transporte Biológico/efectos de los fármacos , Bucladesina/farmacología , Células Cultivadas , Epinefrina/farmacología , Isoproterenol/farmacología , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/efectos de los fármacos , Cinética , Levodopa/sangre , Levodopa/orina , Masculino , Norepinefrina/farmacología , Norepinefrina/orina , Propanolaminas/farmacología , Unión Proteica , Ratas , Ratas Wistar , Terbutalina/farmacologíaRESUMEN
This study assess the effects of glucocorticoids on dopamine excretion and evaluates the participation of renal dopamine in the effects of glucocorticoids on renal function and Na+ excretion. Dexamethasone (i.m.; 0.5 mg/kg) was administered to male Wistar rats on day 2 or on days 2 and 5. Daily urinary excretions of Na+, dihydroxyphenylalanine (DOPA), dopamine and dihydroxyphenylacetic acid were determined from day 1 to day 7. Renal function was evaluated 8 h after dexamethasone administration in a separate group. The first dose of dexamethasone increased about 100% diuresis and natriuresis, increased urinary DOPA and renal plasma flow, and did not affect urinary dopamine or the other parameters evaluated. These effects were not affected by previous administration of haloperidol. The second dexamethasone dose increased about 200% diuresis and natriuresis, increased urinary dopamine, DOPA, dihydroxyphenylacetic acid, Uosm x V and both glomerular filtration rate and renal plasma flow. Carbidopa administered before the second dexamethasone dose blunted both the diuretic and the natriuretic response whereas haloperidol abolished or blunted all the effects of the second dexamethasone dose. These results show that modifications in renal dopamine production produced by corticoids may contribute to the effects of these hormones on Na+ balance and diuresis and suggest that regardless the factor that promotes an increase in renal perfusion and glomerular filtration rate during long term administration of glucocorticoids, a dopaminergic mechanism is actively involved in the maintenance of these hemodynamic changes.
Asunto(s)
Dexametasona/farmacología , Dopamina/biosíntesis , Glucocorticoides/farmacología , Riñón/efectos de los fármacos , Natriuresis/efectos de los fármacos , Ácido 3,4-Dihidroxifenilacético/orina , Animales , Cardiotónicos/farmacología , Dihidroxifenilalanina/orina , Diuresis/efectos de los fármacos , Dopamina/orina , Dopaminérgicos/farmacología , Interacciones Farmacológicas , Tasa de Filtración Glomerular/efectos de los fármacos , Haloperidol/farmacología , Riñón/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
A major proportion of urinary dopamine derives from the renal decarboxylation of circulating dopa. This study evaluates the effects of aging on renal production of dopamine using 3- and 12-mo-old male Wistar rats. Urinary excretion of Na+, norepinephrine (NE), 3,4-dihydroxyphenylglycol, and dopa were similar in the two groups. Urinary dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were lower in older animals (dopamine, 20 +/- 6 vs. 47 +/- 7 nmol/24 h, P < 0.001; DOPAC, 142 +/- 36 vs. 304 +/- 56 nmol/24 h, P < 0.03). Urinary 3-O-methyldopa (OM-dopa) was higher in 12-mo-old rats (6.2 +/- 2.0 vs. 3.3 +/- 0.20 nmol/24 h, P < 0.03). Levels of dopa and NE in renal cortex from 12-mo-old rats were higher (P < 0.001) than in younger animals. Dopamine content in renal cortex from 3-mo-old rats was 295 +/- 64 pmol/g, whereas it was undetectable in 12-mo-old animals. Aromatic-L-amino-acid decarboxylase and monoamine oxidase activities were higher (P < 0.001) in renal cortex from 12-mo-old animals. Catechol-O-methyltransferase activity was similar in both groups. The uptake of dopa by the luminal membrane was explored using brush-border membrane vesicles. The Na(+)-gradient-driven (100 mM) uptake of dopa into vesicles from 3-mo-old animals showed at 10 s an overshoot threefold greater than the equilibrium uptake. The overshoot was blunted in 12-mo-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Envejecimiento/metabolismo , Dihidroxifenilalanina/metabolismo , Dopamina/metabolismo , Riñón/fisiología , Ácido 3,4-Dihidroxifenilacético/orina , Animales , Descarboxilasas de Aminoácido-L-Aromático/metabolismo , Transporte Biológico , Catecol O-Metiltransferasa/metabolismo , Dopamina/orina , Riñón/crecimiento & desarrollo , Corteza Renal/crecimiento & desarrollo , Corteza Renal/fisiología , Masculino , Microvellosidades/metabolismo , Monoaminooxidasa/metabolismo , Norepinefrina/metabolismo , Ratas , Ratas Wistar , Análisis de Regresión , Tirosina/análogos & derivados , Tirosina/orinaRESUMEN
En este trabajo se han compilado los distintos modos cromatográficos y sistemas de detección utilizados en la cromatografía líquida de alta resolución de aminas biogénicas. Se indican las características generales del intercambio catiónico, fase reversa, fase reversa de pares iónicos y cromatografía de partición con fase reversa de pares iónicos. También se analizan comparativamente la detección UV, detección fluorimétrica usando fluorescencia nativa o bien derivatización pre- y postcolumna y detección electroquímica de gran utilidad para esta extensa familia de compuestos. Se dan ejemplos de aplicación de interés en el campo bioquímico-clínico, con el análisis de ácido homovainillínico, ácido 3,4-dihidroxifenilacético y ácido 5-hidroxiindolacético en líquido cefalorraquídeo, metanefrinas, ácido 3,4-dihidroxifenilacético, catecolaminas, ácidos urinarios y 3-metoxi-4-hidroxifenilglicol en orina, catecolaminas y 3-metoxi-4-hidroxifenilglicol en plasma, catecolaminas, 3-metoxi-4-hidroxifenilglicol y otros neurotransmisores en cerebro de rata. Se discuten, también, los tratamientos previos requeridos especialmente para orina y plasma, así como las condiciones de conservación y su incidencia en los resultados obtenidos (AU)