1 Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611; and 2 Centro de Investigación del Cáncer, Universidad de Salamanca, 37007 Salamanca, Spain
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Dopamine (DA) increases lung
edema clearance by regulating vectorial Na+ transport and
Na-K-ATPase in the pulmonary epithelium. We studied the role of the
mitogen-activated protein kinase (MAPK)-extracellular signal-regulated
kinase (ERK) pathway in the DA regulation of Na-K-ATPase in alveolar
epithelial cells (AEC). Incubation of AEC with DA resulted in a rapid
stimulation of ERK activity via dopaminergic type 2 receptors. Analysis
of total RNA and protein showed a 1.5-fold increase in the Na-K-ATPase
1-subunit mRNA levels and up to a fivefold increase in
1-subunit protein abundance after DA stimulation, which
was blocked by the MAPK kinase (MEK) inhibitors PD-98059 and U-0126.
Also, the DA-ERK pathway stimulated the synthesis of a green
fluorescent protein reporter gene driven by the
1-subunit promoter, which indicates that DA regulates the Na-K-ATPase
1-subunit at the transcriptional level.
The DA-mediated increase in
1-subunit mRNA protein
resulted in an increase in functional Na pumps in the basolateral
membranes of alveolar type II cells. These results suggest that the
MAPK-ERK pathway is an important mechanism in the regulation of
Na-K-ATPase by DA in the alveolar epithelium.
alveolar type II cells; green fluorescent protein; transcriptional regulation; basolateral membrane
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
NA-K-ATPASE IS A
UBIQUITOUS enzyme essential for the maintenance of membrane
potential and control of cellular volume (17). It also has
been shown to have an important role in lung edema clearance by
increasing active Na+ transport (4, 23). A
functional Na-K- ATPase is a transmembrane heterodimer protein
composed of two subunits ( and
) (29). The catalytic
-subunit contains the binding sites for Na, K, and ATP. The
glycosylated
-subunit appears to be important in the insertion of
the Na pump to the plasma membrane (20). In alveolar type
II (ATII) cells, Na-K-ATPase is predominantly composed of
1- and
1-isoforms (25).
Na-K-ATPase can be regulated by short-term or long-term mechanisms. The short-term regulation of the Na pump involves changes in its turnover, its affinity for substrates, and/or its abundance at the cell surface (7, 8, 12). The long-term regulation of Na-K-ATPase includes transcriptional activation, translation, and protein stability (12). Aldosterone, insulin, thyroid hormone, epidermal growth factor, and keratinocyte growth factor are some of the agonists known to regulate the transcriptional and/or translational rate of the Na pump, although the molecular mechanisms involved have not yet been elucidated.
Dopamine (DA) inhibits Na-K-ATPase activity in most tissues, including brain (6), vascular bed (24), and kidney (5). In contrast, recent studies have suggested that DA increases the ability of the lungs to clear edema, probably by the regulation of the alveolar epithelial Na-K-ATPase function (1, 27).
The mitogen-activated protein kinase (MAPK)-extracellular
signal-regulated kinase (ERK) cascade is a major signaling system by
which cells transduce extracellular signals into intracellular responses. ERK proteins (ERK1/2) have many substrates, including the
ternary complex factor Elk-1, a member of the Ets family of transcription factors, which is recruited by serum-response factors to
bind serum-response elements, located in the promoters of many early
genes (31) and also in the 5'-flanking region of the
Na-K-ATPase 1-subunit gene (18).
DA has an inhibitory role on the ERK pathway in most cell types (22, 30), although recent reports suggested that DA activates ERK proteins in Chinese hamster ovary cells (32) and neurons (14). However, there are no studies exploring whether the activation of ERK by DA regulates Na-K-ATPase.
We have investigated whether DA activates the ERK signaling pathway in
alveolar epithelial cells (AEC) and whether this activation regulates
Na-K-ATPase. Our results demonstrate that DA regulates 1-subunit mRNA and protein abundance via an
ERK-dependent pathway that involves dopaminergic type 2 receptors
(D2R) but not D1R and that this stimulation
results in an increase in protein abundance in the basolateral
membranes (BLMs) of ATII cells where the Na pump is active and,
consequently, in an increase in Na-K-ATPase activity.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Cell isolation and culture. ATII cells were isolated from pathogen-free male Sprague-Dawley rats as previously described (23, 25). The day of isolation and plating was designated culture day 0. All experimental conditions were tested in day 2 cells.
ERK assay. ATII cells were serum starved for 18-24 h and treated with regulators for the desired time. The ERK activity was determined as phosphorylation of the ERK substrate Elk-1 using a p44/p42 MAPK assay kit (New England Biolabs, Beverly, MA). PD-98059 (New England Biolabs) and U-0126 (Promega, Madison, WI) were used as inhibitors of the ERK activity.
Cloning of the Na-K-ATPase
1-subunit promoter into pEGFP-1 plasmid.
A 786-bp fragment of the Na-K-ATPase
1-subunit gene
promoter region containing 773 bp upstream and 12 bp downstream from the nucleotide +1 was subcloned into the EcoRV site of
plasmid pT7blue(R) (Novagen, Madison, WI) and then subcloned as a
HindIII-EcoRI fragment into the promoter reporter
vector pEGFP-1 (Clontech, Palo Alto, CA). The final construct was named
pEGFP-
1P.
Generation of stable cell lines overexpressing
pEGFP-1P construct.
A549 cells derived from human AEC (American Type Culture Collection CCL
185) were transfected with 2-5 µg of plasmid
pEGFP-
1P by using SuperFect Reagent (QIAGEN, Valencia,
CA) and selected in the presence of 600 µg/ml Geneticin (G418).
RNA isolation and analysis by semiquantitative RT-PCR. Total cellular RNA from ATII cells was isolated by using RNeasy total RNA kit (QIAGEN). The reverse transcription (RT) reaction was performed using the SUPERSCRIPT preamplification system (GIBCO BRL, Grand Island, NY). The resultant cDNAs were amplified by PCR using specific primers and analyzed by agarose gel electrophoresis. The amplified bands were quantified by densitometric scan and normalized against the internal control gene GAPDH (glyceraldehyde-3-phosphate dehydrogenase).
Oligonucleotides and conditions used in PCR.
For the amplification of the Na-K-ATPase 1-subunit, we
used the following set of oligonucleotides: 5'-AAT CAT GAA CGA GGA GAG
CG-3' and 5'-AGG TGA GGT TGG TGA ACT GC-3' that correspond to the
positions 418-437 and 786-805, respectively, of the cDNA from
the rat gene (considering as number 1 the "A" of the first ATG of
the gene). The conditions for the PCR were 94°C, 1 min; 53°C, 1 min
30 s; and 72°C, 2 min for 41 cycles. For the amplification of
the control gene GAPDH, we used the rat GAPDH Control Amplimer Set
(Clontech) at 94°C, 45 s; 60°C, 45 s; and 72°C, 2 min
for 21 cycles. Primers used for the detection of D2R were
5'-CCT TCA CCA TCT CTT GC-3' and 5'-CCT TCT GCT GGG AGA GC-3',
corresponding to positions 488-504 and 1089-1105,
respectively, of the cDNA from the mouse gene, and the conditions for
the PCR were 94°C, 1 min; 53°C, 1 min 30 s; and 72°C, 2 min
for 30 cycles.
Quantitation of green fluorescent protein fluorescence.
pEGFP-1- or pEGFP-1P-expressing A549 cultures were
plated in four-well Permanox chamber slides (Nalge Nunc International, Naperville, IL), starved, and treated with DA or DA plus PD-98059 for
24 h. Cells were fixed by incubation with 4% formaldehyde in PBS for 15 min, washed with PBS, and mounted with Vectashield mounting medium (Vector Laboratories, Burlingame, CA).
Deglycosylation of the Na-K-ATPase
1-subunit protein.
Total protein (100 µg) from ATII cells was digested with 1 U of
N-glycosidase F as described previously (15).
Western blot analysis.
Total deglycosylated protein (100 µg) or 5 µg of BLMs, isolated as
described previously (8), were resolved by 12.5% SDS-PAGE and analyzed by immunoblotting using specific Na-K-ATPase
anti-1 polyclonal antibody or anti-
1
monoclonal antibody (a generous gift from Dr. Martin-Vasallo,
University of La Laguna, Spain, and Dr. M. Caplan, Yale University, CT,
respectively). For the detection of GFP, 25 µg of total protein were
resolved by 12.5% PAGE and analyzed by immunoblotting using an
anti-GFP monoclonal antibody, clone B34 (BABCO, Richmond, CA).
Transport measurements. Ouabain-sensitive 86Rb+ uptake was used to estimate the rate of K+ transport by Na-K-ATPase in AEC. Briefly, cells were preincubated for 5 min at 37°C in a gyratory bath at 100 rpm by adding 5 mM ouabain in HEPES-buffered DMEM. This medium was then removed, and otherwise identical fresh medium containing 1 µCi/ml 86Rb+ was added. After a 5-min incubation (37°C, 100 rpm), uptake was terminated by aspirating the assay medium and washing the plates in ice-cold MgCl2. Plates were allowed to dry, and cells were solubilized in 0.2% SDS. 86Rb+ influx was quantified in aliquots of the SDS extract with a liquid scintillation counter. Protein was quantified in aliquots by the Lowry method.
Statistical analysis. Data are means ± SE. All statistical analyses were made using one-way ANOVA, except data in Figs. 4 and 6 that were treated with two-way ANOVA (time and DA as the 2 independent variables), followed by a multiple comparison test (Tukey) when the F statistic indicated significance. Results were considered significant when P < 0.05.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
DA activates MAPK-ERK in
ATII cells.
Figure 1 shows that DA induced up to
3.5-fold increase in ERK activity after 5 min of incubation of
subconfluent, serum-starved ATII cells. This activation was specific
because it was abolished when cells were pretreated with the specific
MAPK kinase (MEK) inhibitor PD-98059 2 h before DA stimulation.
|
DA stimulates ERK activity via
D2R.
RT-PCR analysis of total RNA showed that D1R
(2) and D2R mRNA are both expressed in ATII
cells (Fig. 2). To determine whether D1R or D2R receptors mediate ERK activation by
DA, serum-starved ATII cells were treated with DA in the presence of
specific D1R and D2R antagonists (Sch-23390 and
S-sulpiride, respectively) or with a D1R agonist
(fenoldopam) and D2R agonists [quinpirole and
R()-propylnorapomorphine hydrochloride (R-NPA)]. As shown in Fig.
3, preincubation with
S-sulpiride (but not with Sch-23390) inhibited the
activation of ERK by DA. Also, D2R activation by quinpirole
or R-NPA, but not by the D1R agonist fenoldopam, stimulated ERK activity in ATII cells.
|
|
DA regulates Na-K-ATPase
1-subunit mRNA and protein abundance in
ATII cells via an ERK-dependent
mechanism.
To determine whether DA regulates Na-K-ATPase at the mRNA and/or
protein level and whether this effect is mediated by ERK activation,
serum-starved ATII cells were incubated with DA in the presence and
absence of the MEK inhibitor PD-98059. Changes in mRNA and protein
levels were examined at different times. As shown in Fig.
4, there was a 1.5-fold increase in the
Na-K-ATPase
1-subunit mRNA levels after ~18 h of DA
stimulation. This increase was abolished in cells preincubated with
PD-98059. The optimal conditions for the PCR of both the Na-K-ATPase
1-subunit gene (41 cycles) and the GAPDH gene (21 cycles) were established in preliminary studies (Fig.
5).
|
|
|
|
DA regulates the transcription of the
Na-K-ATPase 1-subunit.
To determine whether DA regulates the Na-K-ATPase
1-subunit at the transcriptional level, permanent
transfectants of A549 cells expressing pEGFP-
1P or
vector alone were serum starved and treated with DA in the presence and
absence of PD-98059 or U-0126. DA activated ERK in A549 cells to the
same extent as in ATII cells (Fig.
8A). Cells were analyzed by
1) fluorescent microscopy, 2) fluorescent
spectrophotometry, and 3) Western blot with anti-GFP antibodies. The three different approaches showed that DA increased GFP
expression under the control of the Na-K-ATPase
1-subunit promoter (Fig. 8B). The increase
observed in both the fluorometric analysis (Fig. 8B,
b) and the immunoblotting (Fig. 8B, c)
was ~1.5-fold, which agrees with the increase in mRNA detected by PCR
(Fig. 4). The DA-induced increase in GFP expression was inhibited by
PD-98059, as demonstrated by Western blot (Fig. 8B,
c). We found that PD-98059 is autofluorescent, precluding
the ability to evaluate quantitatively its inhibitory effect on
DA-induced GFP expression by fluorometric analysis. Additionally, in
accordance with results in Fig. 3, quinpirole also induced GFP
expression, which was inhibited by U-0126 (Fig. 7C). Taken
together, these results demonstrate that DA regulates Na-K-ATPase
1-subunit at the transcriptional level by an
ERK-dependent mechanism.
|
DA increases Na-K-ATPase protein
abundance and activity in BLMs.
BLMs were isolated from serum-starved ATII cells treated with DA for
24 h in the presence or absence of PD-98059. Immunoblotting with
anti-1 and anti-
1 antibodies showed an
increase in both Na-K-ATPase subunits in BLMs of cells treated with DA
compared with control cells and cells pretreated with PD-98059 (Fig.
9A). This increase in Na pump
abundance at BLMs resulted in an increase in functional pumps;
as shown in Fig. 9B, Na-K-ATPase activity (measured as
86Rb+ uptake) increased in serum-starved ATII
cells 24 h after treatment with DA, an effect prevented by
PD-98059.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The major findings of the present study are that DA regulates
Na-K-ATPase 1-subunit via a long-term mechanism that
results in a functional Na-K-ATPase dimer in the BLMs of AEC and that these events involve D2R but not D1R.
In animal models, the fluid is reabsorbed from the lungs predominantly
by active Na+ transport via the apical Na+
channels and basolateral Na-K-ATPases located in the AEC. There is a
large body of information regarding regulation of Na-K-ATPase in the
kidney but much less is known about its regulation in the alveolar
epithelium. Catecholamines, in particular -adrenergic agonists, have
been shown to regulate Na+ channels and Na-K-ATPase
activity in lung alveolar epithelium (8, 19). Recent
studies have demonstrated that DA stimulates lung edema clearance,
possibly via modulation of Na-K-ATPase in the pulmonary epithelium
(1, 27).
DA-mediated regulation of Na-K-ATPase by short-term mechanisms
has been reported in kidney (5, 7) and brain
(6). We are reporting for the first time that DA
stimulates ERK activity in ATII cells and that this activation results
in the transcriptional regulation and translation of the Na-K-ATPase
1-subunit via a MAPK-ERK-dependent mechanism.
In most systems, DA inhibits Na-K-ATPase activity by short-term mechanisms via the dopaminergic receptors D1R and D2R (5, 6, 14). In the kidney, stimulation of D1R inhibits Na-K-ATPase via the cAMP-protein kinase A pathway (12), a negative regulator of ERK activation (10, 28). On the contrary, DA-mediated D1R activation appears to regulate Na-K-ATPase in AEC within 15 min by short-term regulatory mechanisms (26). However, as shown in Fig. 3, fenoldopam, a D1R agonist, did not alter basal ERK activation, and preincubation of ATII cells with the D1R antagonist Sch-23390 did not affect the stimulation of ERK by DA. In contrast, inhibition of D2R by S-sulpiride, a specific D2R antagonist, resulted in inhibition of DA-stimulated ERK activity. In agreement with these results, stimulation of ATII cells with the D2R agonists quinpirole and R-NPA activated ERK to similar levels as DA. Activation of ERK proteins by D2R stimulation also has been recently described in neuronal tissue (33), but this is the first study showing that activation of ERK via D2R results in transcriptional regulation of Na-K-ATPase.
Our results showing that DA stimulation is associated with augmented
Na-K-ATPase mRNA and protein abundance are similar to a recent report
where -adrenergic agonists increased Na-K-ATPase
1-subunits in AEC (21). However, that study
did not identify the mechanisms regulating this event. In the present
study, the Na-K-ATPase
1-subunit mRNA levels increased
by 1.5-fold after ~18 h of incubation with DA (Fig. 4) without change
in the
1-subunit mRNA levels. This increase is due to
transcriptional activation because it is similar to the increase
observed in GFP synthesis under the control of the
1-subunit promoter (Figs. 7C and
8B). We also found that Na-K-ATPase
1-subunit
protein increased by up to fivefold after incubation with DA (Fig. 6).
The larger increase in protein abundance compared with the mRNA levels
may suggest that DA probably has additional effects at
posttranscriptional or translational levels. In this line, parallel
studies indicate a role of a posttranscriptional rapamycin-sensitive
mechanisms involved in the regulation of the Na-K-ATPase by
-adrenergic agonists (Pesce L, unpublished data). The
existence of posttranscriptional regulatory mechanisms has been
reported previously in the regulation of the Na pump (12).
Our results are consistent with previous studies suggesting that
upregulation of the
1-subunit mRNA can occur without
modification of the Na-K-ATPase
1-subunit mRNA levels
(3, 13, 16). Also, the fact that both
1-
and
1-subunits increase in the BLMs of ATII cells
treated with DA, resulting in increased Na-K-ATPase activity (see Fig.
9), suggests that the DA-mediated regulation of the Na pump is
physiologically relevant. We reason that the increase in
1-subunit in ATII cell BLMs can be due to recruitment of
proteins from intracellular pools as described previously
(8).
In summary, these results demonstrate that in AEC, DA regulates
Na-K-ATPase by ERK proteins via the D2R by a mechanism that involves de novo synthesis of -subunits and possibly recruitment of
preexisting
-subunits. This is the first report that links ERK
activation to Na-K-ATPase regulation. Further studies are needed to
elucidate the posttranscriptional regulatory mechanisms involved in the
DA-mediated Na-K-ATPase regulation.
![]() |
ACKNOWLEDGEMENTS |
---|
We thank Dr. Aparajita Ghosh for technical help and Dr. Eugenio Santos for valuable discussions.
![]() |
FOOTNOTES |
---|
This research was supported in part by National Heart, Lung, and Blood Institute Grant HL-65161 and the American Lung Association of Metropolitan Chicago.
Address for reprint requests and other correspondence: J. I. Sznajder, Pulmonary and Critical Care Medicine, Northwestern Univ., 300 E. Superior St. Tarry 14-707, Chicago, IL 60611 (E-mail: j-sznajder{at}northwestern.edu).
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. Section 1734 solely to indicate this fact.
Received 7 April 2000; accepted in final form 14 February 2001.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Barnard, ML,
Olivera WG,
Rutschman DM,
Bertorello AM,
Katz AI,
and
Sznajder JI.
Dopamine stimulates sodium transport and liquid clearance in rat lung epithelium.
Am J Respir Crit Care Med
156:
709-714,
1997
2.
Barnard, ML,
Ridge KM,
Saldias F,
Friedman E,
Lecuona E,
Meir G,
Guerrero C,
Bertorello AM,
Katz AI,
and
Sznajder JI.
Stimulation of the dopamine 1 receptor increases lung edema clearance.
Am J Respir Crit Care Med
160:
982-986,
1999
3.
Barquin, N,
Ciccolella DE,
Ridge KM,
and
Sznajder JS.
Dexamethasone upregulates Na-K-ATPase in rat alveolar epithelial type 2 cells.
Am J Physiol Lung Cell Mol Physiol
273:
L825-L830,
1997[ISI][Medline].
4.
Berthiaume, Y,
Staub NC,
and
Matthay MA.
Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep.
J Clin Invest
79:
335-343,
1987[ISI][Medline].
5.
Bertorello, A,
and
Aperia A.
Inhibition of proximal tubule Na+-K+-ATPase activity requires simultaneous activation of DA1 and DA2 receptors.
Am J Physiol Renal Fluid Electrolyte Physiol
259:
F924-F928,
1990
6.
Bertorello, A,
Hopefield JF,
Aperia A,
and
Greengard P.
Inhibition of dopamine of Na,K-ATPase activity in neostriatal neurons through D1 and D2 dopamine receptor synergism.
Nature
347:
386-388,
1990[ISI][Medline].
7.
Bertorello, AM,
and
Katz AI.
Short-term regulation of renal Na-K-ATPase activity: physiological relevance and cellular mechanisms.
Am J Physiol Renal Fluid Electrolyte Physiol
265:
F743-F755,
1993
8.
Bertorello, AM,
Ridge KM,
Chibalin AV,
Katz AI,
and
Sznajder JI.
Isoproterenol increases Na+-K+-ATPase activity by membrane insertion of subunits in lung alveolar cells.
Am J Physiol Lung Cell Mol Physiol
276:
L20-L27,
1999
9.
Brodde, OE.
Vascular dopamine receptors: demonstration and characterization by in vitro studies.
Life Sci
31:
289-306,
1982[ISI][Medline].
10.
Cook, SJ,
and
McCormick F.
Inhibition by cAMP of Ras-dependent activation of Raf.
Science
262:
1069-1072,
1993[ISI][Medline].
11.
Daaka, Y,
Luttrell LM,
and
Lefkowitz RJ.
Switching of the coupling of the 1 adrenergic receptor to different G proteins by protein kinase A.
Nature
390:
88-91,
1997[ISI][Medline].
12.
Ewart, HS,
and
Klip A.
Hormonal regulation of the Na+-K+-ATPase: mechanisms underlying rapid and sustained changes in pump activity.
Am J Physiol Cell Physiol
269:
C295-C311,
1995
13.
Factor, P,
Senne C,
Dumasius V,
Ridge K,
Jaffe HA,
Uhal B,
Gao Z,
and
Sznajder JI.
Overexpression of the Na,K-ATPase alpha1 subunit increases Na,K-ATPase function in A549 cells.
Am J Respir Cell Mol Biol
18:
741-749,
1998
14.
Huff, RM.
Signal transduction pathways modulated by the D2 subfamily of dopamine receptors.
Cell Signal
8:
453-459,
1996[ISI][Medline].
15.
Lecuona, E,
Luquin S,
Avila J,
Garcia-Segura LM,
and
Martin-Vasallo P.
Expression of the 1 and
2 (AMOG) subunits of the Na,K-ATPase in neuronal tissues: cellular and developmental distribution patterns.
Brain Res Bull
40:
167-174,
1996[ISI][Medline].
16.
Lescale-Matys, L,
Hensley CB,
Crnkovic-Markovic R,
Putnam DS,
and
McDonough AA.
Low K+ increases Na,K-ATPase abundance in LLC-PK1/Cl4 cells by differentially increasing , and not
, subunit mRNA.
J Biol Chem
265:
17935-17940,
1990
17.
Lingrel, JB,
and
Kuntzweiler T.
Na+, K(+)-ATPase.
J Biol Chem
269:
19659-19662,
1994
18.
Liu, B,
and
Gick G.
Characterization of the 5' flanking region of the rat Na,K-ATPase beta 1 subunit gene.
Biochim Biophys Acta
1130:
336-338,
1992[ISI][Medline].
19.
Matalon, S,
Benos DJ,
and
Jackson RM.
Biophysical and molecular properties of amiloride-inhibitable Na+ channels in alveolar epithelial cells.
Am J Physiol Lung Cell Mol Physiol
271:
L1-L22,
1996
20.
McDonough, AA,
Geering K,
and
Farley RA.
The sodium pump needs its subunit.
FASEB J
4:
1598-1605,
1990
21.
Minakata, Y,
Suzuki S,
Grygorczyk C,
Dagenais A,
and
Berthiaume Y.
Impact of -adrenergic agonist on Na+ channel and Na+-K+-ATPase expression in alveolar type II cells.
Am J Physiol Lung Cell Mol Physiol
275:
L414-L422,
1998
22.
Ohmichi, M,
Koike K,
Nohara A,
Kanda Y,
Sakamoto T,
Zhang ZX,
Hirota K,
and
Miyake A.
Dopamine inhibits TRH-induced MAP kinase activation in dispersed rat anterior pituitary cells.
Biochem Biophys Res Commun
201:
642-648,
1994[ISI][Medline].
23.
Olivera, W,
Ridge K,
Wood LDH,
and
Sznajder JI.
Active sodium transport and alveolar epithelial Na-K-ATPase increase during subacute hyperoxia in rats.
Am J Physiol Lung Cell Mol Physiol
266:
L577-L584,
1994
24.
Rashed, SMK,
and
Songu-Mize E.
Regulation of Na(+)-pump activity by dopamine in rat tail arteries.
Eur J Pharmacol
284:
289-297,
1995[ISI][Medline].
25.
Ridge, K,
Rutschman DH,
Factor P,
Katz AI,
Bertorello AM,
and
Sznajder JI.
Differential expression of Na-K-ATPase isoforms in rat alveolar epithelial cells.
Am J Physiol Lung Cell Mol Physiol
273:
L246-L255,
1997
26.
Ridge, KM,
Guerrero C,
Lecuona E,
Gare M,
Bertorello AM,
Katz AI,
and
Sznajder JI.
Dopamine upregulates alveolar epithelial cell Na,K-ATPase via a protein kinase C pathway (Abstract).
Am J Respir Crit Care Med
157:
A853,
1998.
27.
Saldias, FJ,
Lecuona E,
Comellas AP,
Ridge KM,
and
Sznajder JI.
Dopamine restores lung ability to clear edema in rats exposed to hyperoxia.
Am J Respir Crit Care Med
159:
626-633,
1999
28.
Schramm, K,
Niehof M,
Radziwill G,
Rommel C,
and
Moeling K.
Phosphorylation of c-RAF-1 by protein kinase A interferes with activation.
Biochem Biophys Res Commun
201:
740-747,
1994[ISI][Medline].
29.
Skou, JC,
and
Esmann M.
The Na,K-ATPase.
J Bioenerg Biomembr
24:
249-261,
1992[ISI][Medline].
30.
Voyno-Yasenetskaya, TA,
Faure MP,
Ahn NG,
and
Bourne HR.
G12 and G13 regulate extracellular signal-regulated kinase and c-Jun kinase pathways by different mechanisms in COS-7 cells.
J Biol Chem
271:
21081-21087,
1996
31.
Wasylyk, B,
Hagman J,
and
Gutierrez-Hartmann A.
Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling pathway.
Trends Biochem Sci
23:
213-216,
1998[ISI][Medline].
32.
Welsh, GI,
Hall DA,
Warnes A,
Strange PG,
and
Proud CG.
Activation of microtubule-associated protein kinase (Erk) and p70 S6 kinase by D2 dopamine receptors.
J Neurochem
70:
2139-2146,
1998[ISI][Medline].
33.
Yan, Z,
Feng J,
Fienberg AA,
and
Greengard P.
D2 dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons.
Proc Natl Acad Sci USA
96:
11067-11612,
1999