Centro de Investigaciones Endocrinológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, 1425 Buenos Aires, Argentina
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
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 (Km 0.316 vs 1.53 µM). L-Dopa uptake was decreased by the
nonselective adrenergic agonists epinephrine or norepinephrine (40%),
by the -selective agonist isoproterenol or the
2-selective agonist terbutaline (60%), but not by
-selective agonists (all 1 µM). The effect of
norepinephrine, isoproterenol, or terbutaline was unaffected by
addition of the
1-antagonist atenolol, abolished by
ICI-118,551, a
2-antagonist (both 0.1 µM), and
mimicked by the addition of dibutyryl-cAMP (1 µM). Preincubation with
terbutaline decreased the number of high-affinity uptake sites
(Vmax = 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 µM). 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
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.
L-3,4-dihydroxyphenylalanine; catecholamines; cellular transport; kidney
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
L-3,4-DIHYDROXYPHENYLALANINE (L-dopa) is the immediate product of the rate-limiting step in catecholamine biosynthesis and the precursor of all the endogenous catecholamines (15). Circulating L-dopa is removed by the kidney, and a major proportion of dopamine in rat and human urine derives from the renal decarboxylation in proximal tubular cells of L-dopa reabsorbed from ultrafiltrated plasma (17, 20, 29). Several lines of evidence indicate that renal dopamine plays an important role in the regulation of salt balance acting locally as an autocrine-paracrine substance (1, 11, 20). Renal production of dopamine is dependent on substrate availability, on the uptake of L-dopa into tubular epithelial cells, and on the activity of aromatic L-amino acid decarboxylase (AADC), the enzyme responsible for the conversion of L-dopa into dopamine. Several studies performed in renal tissues have failed to demonstrate parallel changes in the activity of AADC and the production of dopamine and suggested that the uptake of L-dopa is the rate-limiting process in dopamine formation (2, 20).
It is well established that the nephron reabsorbs L-amino acids almost completely from the glomerular filtrate and that the reabsorption occurs mainly in the proximal tubule (7, 30). Early studies have demonstrated that the reabsorption of L-dopa in the proximal convoluted tubules is an active process, independent of the AADC activity, with great structural specificity (6). In a previous study, using brush-border membrane vesicle preparations, we have characterized the transport of L-dopa as an Na+-dependent cotransport, which is impaired in aged rats (2). However, only scant biochemical detail is available on the transport of L-dopa and of other L-amino acids in the kidney, and the regulation of this process is still poorly understood.
The adrenergic nervous system modulates several aspects of kidney
function. The kidney has large numbers of unevenly distributed adrenergic receptors, and it has been suggested that these receptors may subserve specific functions in the different kidney zones. Adrenergic receptors of the 1-,
2-,
1-, and
2-subtypes have been
characterized in rat renal proximal tubules (22,
27) and have been shown to be involved in the modulation
of tubular transport (19, 23,
24). In tissues other than the kidney, adrenergic
receptors have been shown to be implicated in the regulation of the
transport of sugars (4, 5, 13)
and amino acids (10, 21).
This study was aimed to assess the role of adrenergic receptors on the
regulation of the uptake of L-dopa and therefore on the
production of dopamine by renal tubular cells. The present results show
that the uptake of L-dopa by isolated rat renal tubular cells is decreased by 2-adrenergic stimulation but not
affected by
- or
1-receptor stimulation.
Subsequently, to provide evidence for the presence of this regulatory
mechanism in in vivo conditions, we assessed the effects of
administration of a
2-adrenergic receptor antagonist to
intact animals.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Chemicals.
L-Dopa, collagenase (type IV), DMEM, norepinephrine,
epinephrine, N,2'-O-dibutyryl-cAMP,
3-methoxy-DL-tyrosine, isoproterenol, terbutaline,
methoxamine, atenolol, and phentolamine, were obtained from Sigma
Chemical (St. Louis, MO); 3-hydroxybenzylhydrazine (an AADC inhibitor),
prazosin, and ICI-118,551 (a selective 2-antagonist) were obtained from Research Biochemicals International (Natick, MA);
and octopamine was obtained from Calbiochem (San Diego, CA).
Animals. Three-month male Wistar rats weighing between 250 and 300 g were used in this study. All animals were inbred in our laboratory, kept at 22°C on a 12:12-h dark-light cycle, and given free access to normal rat diet (protein content 25%) and tap water.
Preparation of proximal tubule cell suspension. Proximal tubule cells suspensions were prepared as previously described (3). Briefly, rats were killed by decapitation, and the kidneys were rapidly removed and rinsed free from blood with saline (0.9% wt/vol NaCl solution). The kidneys were placed on an ice-cold glass plate, and the cortex was isolated. Thereafter, the tissue was minced on ice to a paste-like consistency. The cortical tissue was digested with 0.7 mg/ml collagenase (type IV, Sigma) in 10 ml DMEM supplemented with 20 mM HEPES and 24 mM NaHCO3 (pH 7.4). Incubation was carried out in a shaking water bath at 37°C for 30 min in an atmosphere of 95% O2-5% CO2. It was cooled on ice and poured through graded sieves (180, 75, 53, and 38 µm in pore size) to obtain a cell suspension. This suspension contains mostly proximal tubular cells (3). To separate the remaining blood cells and traces of collagenase, the cell suspension was centrifuged at 400 rpm for 4 min and washed, and the final pellet was resuspended in Krebs buffer. Each determination was performed using 50 µl of the cell suspension containing 150-250 µg protein. The cells were used within 2 h of preparation and kept on ice until studied. The quality of each preparation was monitored by microscopy, and the viability was assessed by Trypan blue exclusion. Protein concentration was measured by the method of Lowry, with bovine serum albumin as a standard.
Transport of L-dopa into isolated proximal tubular
cells.
The transport of L-dopa was determined using a modification
of a previously described method (2). Briefly, cells were
preincubated for 20 min in Krebs buffer (in mM: 120 NaCl, 4.7 KCl, 1.2 MgSO4, 2.4 CaCl2, 24 NaHCO3, 1.2 KH2PO4, 0.5 EDTA, 0.57 ascorbic acid, and 11 glucose, pH 7.4) with the addition of 3-hydroxybenzylhydrazine (250 µM) to inhibit the AADC activity, in the absence or presence of
3-methoxy-L-tyrosine (3-O-methyldopa, 100 µM), isoproterenol, norepinephrine, epinephrine, terbutaline,
octopamine, methoxamine (all 1 µM), atenolol, or ICI-118,551 (both
0.1 µM), or increasing concentrations of isoproterenol or
dibutyryl-cAMP (both 1 nM to 1 µM). In experiments performed to test
the influence of Na+ on L-dopa uptake, cells
were incubated in Krebs buffer (144 mM Na+, 6 mM
K+) or in lower Na+ Krebs buffer (44 mM
Na+, 106 mM K+). L-Dopa uptake was
started by the addition of the indicated concentrations of
L-dopa to the incubation medium. Unless specified, the
preincubation and incubation reactions were carried out for 20 min at
room temperature. During preincubation and incubation, cells were
continuously shaken. Reactions were stopped by centrifugation (4°C,
600 rpm, 3 min) and rapid removal of uptake solution by means of a
vacuum pump connected to a Pasteur pipette followed by immediate
rinsing twice with ice-cold Krebs solution and centrifuged (4°C, 600 rpm, 3 min). The pellet was resuspended in 200 µl of 0.3 N
HClO4, disrupted (Sonifier Cell Disruptor, model w185; Heat Systems-Ultrasonics), and stored at 20°C until assayed.
Production of dopamine by isolated proximal tubular cells.
In experiments aimed to study the accumulation of newly formed dopamine
in the incubation medium, isolated tubular cells were preincubated in
the same conditions as described above, with the exception that the
AADC inhibitor was not added. Cells were preincubated in the absence or
presence of norepinephrine or terbutaline (both 1 µM), or atenolol or
ICI-118,551 (both 0.1 µM). Reactions were started by
incubation with L-dopa (200 nM, 20 min) and were stopped by
centrifugation (4°C, 600 rpm, 3 min). The incubation medium was
immediately collected on 200 µl of 0.3 N HClO4 and stored at 20°C until assay.
Urine and plasma collection.
On the day of the study, rats were given ICI-118,551 (1.5 mg/kg ip,
twice, every 12 h starting at 9.00 AM) or vehicle and placed in
metabolic cages for 24-h urine collection. Urine was collected into
100-ml polyethylene tubes containing 500 µl of 6 N HCl. Samples were
stored at 20°C until assayed for catechols and creatinine. Blood
samples were obtained from the tail from vehicle or ICI-118,551-treated
animals. Plasma was immediately separated from blood cells by
centrifugation (6,000 rpm, 10 min) and stored frozen until assayed for
L-dopa concentration.
Catechol assays. The catechols in 20-µl aliquots of urine, 250 µl of plasma, 200 µl of cell homogenates, or 500 µl of incubation medium were determined as reported previously (2). Briefly, catechols in the samples were partially purified by batch alumina extraction, separated by reverse-phase high-pressure liquid chromatography using a 4.6 × 250-mm Zorbax RxC18 column (DuPont) and quantified amperometrically by the current produced upon exposure of the column effluent to oxidizing and then reducing potentials in series using a triple-electrode system (ESA, Bedford, MA). Recovery through the alumina extraction step averaged 70-80% for dopamine, 45-55% for L-dopa and 3,4-dihydroxyphenylglycol (DHPG) and 40% for 3,4-dihydroxyphenylacetic acid (DOPAC). Catechol concentrations in each sample were corrected for recovery of an internal standard, dihydroxybenzylamine. Levels of L-dopa, DHPG, and DOPAC were further corrected for differences in recovery of the internal standard and of these catechols in a mixture of external standards. The limit of detection was about 15 pg/volume assayed for each catechol.
Data analysis. Data are means ± SE. Statistical comparisons between two groups were done by Mann-Whitney U Test. Comparisons among several groups were done by analysis of variance (ANOVA) followed by Newman-Keuls test. P < 0.05 defined statistical significance. The lines of the Scatchard plots were determined by linear regression, and the coefficients of linear regression (r) were 0.80 or better in all cases. Km and Vmax were calculated from Scatchard plots.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Figure 1 shows the time dependency
of the uptake of L-dopa into isolated rat renal tubular
cells. In our experimental conditions, intracellular L-dopa
content reached maximal levels after 15-min incubation. Figure 1 also
shows that the addition of 100 µM 3-O-methyldopa, an amino
acid structurally similar to L-dopa, to the incubation medium reduced by 90% the uptake of L-dopa into isolated
cells.
|
The uptake of L-dopa by isolated cells was reduced by 37 ± 7% when the Na+ concentration in the incubation medium was decreased from 144 to 44 mM.
Figure 2 shows that the uptake of
L-dopa into cells in the presence of increasing
concentrations of L-dopa (100 nM to 100 µM) in the
incubation medium was concentration dependent, reaching its maximal
levels at 10 µM L-dopa. Scatchard analysis of the saturation curve showed two different sites for the uptake of L-dopa by these cells, one site with high affinity
(Km = 316 nM) and a
Vmax of 1.22 pmol · mg
protein1 · min
1, and a second site
with a lower affinity (Km = 1.53 µM) and
a Vmax of 2.45 pmol · mg
protein
1 · min
1 (Fig.
3).
|
|
Preincubation of the cells with the nonselective adrenergic agonists
norepinephrine or epinephrine (1 µM) decreased L-dopa uptake by 40% (P < 0.02). The same concentration of
the -selective agonists isoproterenol or terbutaline reduced
L-dopa uptake by 60% (P < 0.01). On the
other hand, the
-selective agonists methoxamine or octopamine (1 µM) had no significant effect. The effect of norepinephrine and
epinephrine on L-dopa uptake was not affected by the
presence of the
-adrenergic antagonists phentolamine or prazosin
(0.1 µM) (Table 1).
|
Preincubation of the cells with different concentrations (1 nM to 1 µM) of isoproterenol demonstrated that the inhibitory effect of the
-selective agonist on L-dopa uptake was dose dependent (Fig. 4).
|
The effect of 1 µM isoproterenol, terbutaline, or norepinephrine was
not reversed by the presence of the 1-adrenergic
antagonist atenolol (0.1 µM) in the incubation medium but was
completely abolished by 0.1 µM ICI-118,551, a
2-adrenergic antagonist (Fig. 5).
|
The effect of 1 µM terbutaline was tested at different concentrations
of L-dopa in the medium (100 nM to 1 µM). Scatchard analysis of the saturation curves in the absence and presence of
terbutaline showed a clear decrease in the number of high-affinity uptake sites (1.10 ± 0.28 vs. 0.52 ± 0.06 pmol · mg
protein1 · min
1; P < 0.02) with no changes in the Km (416 ± 42 vs. 407 ± 38 nM) (Fig. 6). A
time course study of the effect of addition of terbutaline to the
incubation medium showed that the maximal inhibitory effect was
achieved at 20 min (Fig. 7).
|
|
Addition of increasing concentrations (1 nM to 1 µM) of the cAMP
analog dibutyryl-cAMP (dcAMP) also decreased, dose dependently, L-dopa uptake (Table 2).
|
As expected, the incubation of cells with L-dopa (200 nM to
10 µM) produced a dose-dependent increase of dopamine in the medium (Fig. 8). The production of dopamine by
cells incubated with L-dopa (200 nM) was decreased
(P < 0.04) by preincubation with either the
nonselective adrenergic agonist norepinephrine or the
2-selective agonist terbutaline (both at 1 µM). The
decrease of dopamine production elicited by both norepinephrine and
terbutaline were not significantly affected by atenolol but were
antagonized by the presence in the medium of ICI-118,551 (Table
3).
|
|
Administration of ICI-118,551 to intact animals (1.5 mg/kg, twice a
day, 24 h) reduced significantly (P < 0.05) the
urinary excretion of L-dopa, and although it did not change
urinary dopamine, it increased significantly (P < 0.05) the excretion of the deaminated metabolite of dopamine, DOPAC
(Fig. 9). There was no difference in
urinary volume, urinary excretion of Na+, norepinephrine
excretion, the excretion of the deaminated metabolite of
norepinephrine, DHPG, or plasma levels of L-dopa between
control and treated animals (Table 4).
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
This study shows that the uptake of L-dopa into renal
tubular cells, and consequently the production of dopamine by these cells, is inhibited by stimulation of 2-adrenergic
receptors. Our results also provide evidence of the presence of this
regulatory mechanism in the intact animal as well.
Since cell lines do not always maintain the morphological and biochemical characteristics of their parent cells (14), we chose to use freshly isolated proximal tubular cells to optimize the analysis of receptor function. The regulation of the uptake of L-dopa should be demonstrated at concentrations within the physiological range to be considered crucial in the modulation of renal dopamine synthesis. For this reason, we have studied the transport of L-dopa into isolated rat renal proximal tubular cells at concentrations lower than those used by other authors (9, 25, 26, 28). The rationale for the use of lower concentrations of L-dopa is based on two facts. First, L-dopa concentration in rat and human plasma is about 10 nM (Ref. 17 and present results). Because L-dopa is reabsorbed from ultrafiltrated plasma, the concentration of the amino acid in the luminal fluid cannot be higher than the plasma concentration. Second, using brush-border membrane vesicles, we have previously studied the uptake of L-dopa by the luminal membrane. In this preparation, the uptake of L-dopa into vesicles was found to have a Km of about 1 µM (2). In the experimental conditions used in the present study, Scatchard analysis of L-dopa uptake into isolated proximal tubular cells revealed two uptake sites for the amino acid, one with high affinity and low capacity and the other with a lower affinity and a higher capacity. The high-affinity and low-capacity site described here has a Km of the same order of magnitude as the uptake site we have already described using rat renal brush-border membrane vesicles (2). Whether these two sites are identical remains an open question.
Other studies have analyzed the uptake of L-dopa in slices
of renal cortex (12), microdissected renal proximal
tubules (25), LLC-PK1 cells, a porcine-derived
proximal renal tubule epithelial cell line (9,
26), and in OK cells, an epithelial cell line derived from
the kidney of a female American opossum (28). All these
studies were performed in the presence of micromolar to millimolar
concentrations of L-dopa and reported
Km values for the transport of the amino acid
from 50 to 247 µM and Vmax values from 0.2 to
5 nmol · mg protein1 · min
1.
The data reported by other authors and the results from the present
study suggest that the transport of L-dopa into renal tubular cells involves more than one transport system, as has been
described for the tubular transport of other amino acids (18). If this was the case, studies performed at different
L-dopa concentrations could reflect the activity of
different transport systems.
The presence in the incubation medium of nonselective adrenergic
agonists or a nonselective -agonist decreased L-dopa
uptake by tubular cells. This effect was reversed by the addition to the medium of a
2-antagonist, suggesting that it is
mediated by a
2-adrenergic receptor. Moreover, the
stimulation of
2-receptors by terbutaline decreased
L-dopa uptake into and the production of dopamine by
tubular cells in vitro. The effect on L-dopa uptake was
mimicked by the addition of dibutyryl-cAMP, a nonhydrolyzable analog of
cAMP, the second messenger triggered upon stimulation of
2-adrenergic receptors.
Structurally similar compounds could potentially compete for a common
transporter and result in a reduction in L-dopa uptake. This, however, does not seem to be a likely explanation for the inhibitory effect on L-dopa uptake we are reporting here,
since 1) only the nonselective or 2-selective
adrenergic agonists, but not the
-selective agonists, elicited an
effect; 2) the effect was mimicked by the second messenger
cAMP; 3) it was antagonized only by a
2-antagonist; and 4) the time course of the
inhibition of the uptake is not compatible with a competitive effect.
2-Adrenergic receptors have been identified in renal
tubular cells (22), but the physiological role of these
receptors in proximal tubules is not completely understood. These
results provide evidence for a role of
2-receptors in
the modulatory mechanisms contributing to the regulation of the
intracellular availability of the dopamine precursor. A role of
-adrenergic receptors on uptake of L-dopa was ruled out
since neither the inhibitory response to nonselective adrenergic
agonists was affected by the presence of selective
-adrenergic
antagonists nor the selective
-adrenergic agonists used had any
demonstrable effect.
Few studies have described the short-term regulation of amino acid
transport in tubular cells. Changes in plasma membrane amino acid
transport activity have been suggested to result from translocation of
carriers to and from intracellular stores that may represent reserve
pools (18). Thus increased amino acid transport activity
appeared to result from the recruitment of additional preformed
carriers from intracellular pools (8, 16). As
demonstrated by the analysis of the saturation curve obtained in the
presence of terbutaline, a 2-receptor agonist, the
decrease in the uptake of L-dopa was associated with a
decrease in the number of high-affinity uptake sites without changes in the affinity constant. It is tempting to speculate that stimulation of
2-adrenergic receptors could trigger the translocation
of L-dopa carriers from the plasma membrane to
intracellular pools, resulting in both the decreased number of uptake
sites but also in the decreased uptake of the amino acid we report here.
In line with the observations in vitro, the administration of the
2-antagonist ICI-118,551 to intact animals resulted in decreased urinary L-dopa and increased excretion of the
dopamine metabolite DOPAC without significant changes in plasma
L-dopa levels. Since a significant fraction of urinary
DOPAC derives from the metabolization of renal dopamine
(29) these effects are consistent with increased
L-dopa uptake, and consequently increased dopamine
formation, when stimulation of
2-receptors is impaired.
An alternative explanation for the increased urinary DOPAC excretion in
treated rats would be that ICI-118,551 inhibited catechol-o-methyl transferase activity switching
catecholamine metabolism from the methylated to the deaminated
metabolites. This hypothesis is unlikely since the excretion of the
deaminated metabolite of norepinephrine DHPG was not altered in
ICI-118,551-treated rats. Thus our results are consistent with
increased L-dopa uptake when stimulation of
2-receptors is impaired, supporting the modulatory role
of these receptors on the uptake of L-dopa in vivo.
In conclusion, the present results provide in vitro and in vivo
evidence of the modulation by 2-adrenergic receptors of
the nonneuronal synthesis of dopamine in proximal tubular cells.
![]() |
ACKNOWLEDGEMENTS |
---|
We thank Dr. Selva Cigorraga and Dr. Eliana Pellizari for helpful discussions.
![]() |
FOOTNOTES |
---|
This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Grant PIP 0573 and by Agencia Nacional de Promoción Científica y Tecnológica PICT 05-00000-0916. M. Barontini, I. Armando, and S. Nowicki are Senior Investigators of CONICET.
Address for reprint requests and other correspondence: I. Armando, Centro de Investigaciones Endocrinologicas, CONICET, Hospital de Niños "R. Gutierrez", Gallo 1330 (1425), Buenos Aires, Argentina.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Received 7 April 1999; accepted in final form 3 February 2000.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Aperia, A,
Bertorello A,
and
Seri I.
Dopamine causes inhibition of Na+/K+-ATPase activity in rat proximal convoluted tubule segments.
Am J Physiol Renal Fluid Electrolyte Physiol
252:
F39-F45,
1987
2.
Armando, I,
Nowicki S,
Aguirre J,
and
Barontini M.
A decreased tubular uptake of dopa results in defective renal dopamine production in aged rats.
Am J Physiol Renal Fluid Electrolyte Physiol
268:
F1087-F1092,
1995
3.
Bertorello, AM.
Diacylglycerol activation of protein kinase C results in a dual effect on Na+,K+-ATPase activity from intact renal proximal tubule cells.
J Cell Sci
101:
343-347,
1992[Abstract].
4.
Bihler, I,
Sawh PC,
and
Sloan IG.
Dual effect of adrenalin on sugar transport in rat diaphragm muscle.
Biochim Biophys Acta
510:
349-360,
1978[ISI][Medline].
5.
Carpéné, C,
Chalaux E,
Lizarbe M,
Estrada A,
Mora C,
Palacin M,
Zorzano A,
Lafontan M,
and
Testar X.
Beta 3-adrenergic receptors are responsible for the adrenergic inhibition of insulin-stimulated glucose transport in rat adipocytes.
Biochem J
296:
99-105,
1993[ISI][Medline].
6.
Chan, YL.
Cellular mechanisms of renal tubular transport of L-dopa and its derivatives in the rat: microperfusion studies.
J Pharmacol Exp Ther
199:
17-24,
1976[Abstract].
7.
Chan, YL,
and
Huang KC.
Microperfusion studies on renal tubular transport of tryptophan derivates in rats.
Am J Physiol
221:
575-579,
1971[ISI][Medline].
8.
Dawson, DW,
and
Cook JS.
Protein kinase C, a system amino acid transport and exocytosis in LLC-PK1 cells (Abstract).
Fed Proc
44:
646,
1985[ISI].
9.
Dawson, R, Jr,
Felheim R,
and
Phillips IM.
Characterization of the synthesis and release of dopamine on LLC-PK1 cells.
Renal Physiol Biochem
17:
85-100,
1994[ISI][Medline].
10.
Edwards, DJ,
Sorisio AD,
and
Knopf S.
Effects of the 2-adrenoceptor agonist clenbuterol on tyrosine and tryptophan in plasma and brain of the rat.
Biochem Pharmacol
38:
2957-2965,
1989[ISI][Medline].
11.
Felder, CC,
Campbell T,
Albrecht F,
and
Jose PA.
Dopamine inhibits Na+-H+ exchanger activity in renal BBMV by stimulation of adenylate cyclase.
Am J Physiol Renal Fluid Electrolyte Physiol
259:
F297-F303,
1990
12.
Fernandes, MH,
Pestana M,
and
Soares-da-Silva P.
Deamination of newly-formed dopamine in rat renal tissues.
Br J Pharmacol
102:
778-782,
1991[Abstract].
13.
Fischer, Y,
Thomas J,
Holman GD,
Rose H,
and
Kammermeier H.
Contraction-independent effects of catecholamines on glucose transport in isolated rat cardiomyocytes.
Am J Physiol Cell Physiol
270:
C1204-C1210,
1996
14.
Freshney, RI.
Animal Cell Cultures. Oxford: Oxford University Press, 1994, p. 1-14.
15.
Goldstein, DS.
Stress, Catecholamines, and Cardiovascular Disease. Oxford: Oxford University Press, 1995, p. 266-269.
16.
Goshima, K,
Masuda A,
and
Owaribe K.
Insulin-induced formation of ruffling membranes of KB cells and its correlation with the enhancement of amino acid transport.
J Cell Biol
98:
801-809,
1984[Abstract].
17.
Grossman, E,
Hoffman A,
Armando I,
Abassi Z,
Kopin IJ,
and
Goldstein DS.
Sympathoadrenal contribution to plasma dopa (3,4-dihydroxyphenylalanine) in rats.
Clin Sci (Colch)
83:
65-74,
1992[ISI][Medline].
18.
Hensley, CB,
and
Mircheff AK.
Complex subcellular distribution of sodium-dependent amino acid transport systems in kidney cortex and LLC-PK1/Cl4 cells.
Kidney Int
45:
110-122,
1994[ISI][Medline].
19.
Ibarra, F,
Aperia A,
Svensson L,
Eklof A,
and
Greengard P.
Bidirectional regulation of Na+,K+-ATPase activity by dopamine and an -adrenergic agonist.
Proc Natl Acad Sci USA
90:
21-24,
1993[Abstract].
20.
Lee, MR.
Dopamine and the kidney: ten years on.
Clin Sci (Colch)
84:
357-375,
1993[ISI][Medline].
21.
Leoni, S,
Spagnuolo S,
Dini L,
Massimi M,
and
Conti Devirgiliis L.
Regulation of amino acid transport in hepatocytes isolated from adult and old rats.
Mech Ageing Dev
46:
19-27,
1988[ISI][Medline].
22.
Meister, B,
Dagerlind A,
Nicholas AP,
and
Hokfelt T.
Patterns of messenger RNA expression for adrenergic receptor subtypes in the rat kidney.
J Pharmacol Exp Ther
268:
1605-1611,
1994[Abstract].
23.
Osborn, JL,
Holdaas H,
Thames MD,
and
Di Bona GF.
Renal adrenoceptor mediation of antinatriuretic and renin responses to low frequency renal nerve stimulation in the dog.
Circ Res
53:
298-305,
1983[ISI][Medline].
24.
Parini, A,
Coupry I,
Laude D,
Diop L,
Vincent M,
Sassard J,
and
Dausse JP.
Noradrenaline content and adrenergic receptors in kidney and heart of the prehypertensive and hypertensive Lyon rat strain.
Am J Hypertens
2:
140-145,
1988.
25.
Soares-da-Silva, P,
Fernandes MH,
and
Pinto-do-Ó PC.
Cell inward transport of L-dopa and 3-O-methyl-L-dopa in rat renal tubules.
Br J Pharmacol
112:
611-615,
1994[Abstract].
26.
Soares-da-Silva, P,
Serrao MP,
and
Vieira-Cohello MA.
Apical and basolateral uptake and intracellular fate of dopamine precursor L-dopa in LLC-PK1.
Am J Physiol Renal Physiol
274:
F243-F251,
1998
27.
Sundaresan, PR,
Fortin TL,
and
Kelvie SL.
Alpha- and beta-adrenergic receptors in proximal tubules of rat kidney.
Am J Physiol Renal Fluid Electrolyte Physiol
253:
F848-F856,
1987
28.
Vieira-Cohello, MA,
and
Soares-da-Silva P.
Apical and basal uptake of L-dopa and L-5-HTP and their corresponding amines, dopamine and 5-HT, in OK cells.
Am J Physiol Renal Physiol
272:
F632-F639,
1997
29.
Wolfovitz, E,
Grossman E,
Folio CJ,
Keiser HR,
and
Kopin IJ.
Derivation of urinary dopamine from plasma dihydroxyphenylalanine (DOPA) in humans.
Clin Sci (Colch)
84:
549-557,
1993[ISI][Medline].
30.
Young, JA,
and
Freedman BS.
Renal tubular transport of amino acids.
Clin Chem
17:
245-266,
1971
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Visit Other APS Journals Online |