Store-operated calcium influx inhibits renin secretion
Frank
Schweda1,
Günter A. J.
Riegger2,
Armin
Kurtz1, and
Bernhard K.
Krämer2
1 Institut für Physiologie I and 2 Klinik und
Poliklinik für Innere Medizin II, Universität
Regensburg, D-93040 Regensburg, Germany
 |
ABSTRACT |
On the
basis of evidence that changes in the extracellular concentration
of calcium effectively modulate renin secretion from renal
juxtaglomerular cells, our study aimed to determine the effect of
calcium influx activated by depletion of intracellular calcium stores
on renin secretion. For this purpose we characterized the effects of
the endoplasmatic Ca2+-ATPase inhibitors thapsigargin (300 nM) and cyclopiazonic acid (20 µM) on renin secretion from
isolated perfused rat kidneys. We found that Ca2+-ATPase
inhibition caused a potent inhibition of basal renin secretion as well
as renin secretion activated by isoproterenol, bumetanide, and by a
fall in the renal perfusion pressure. The inhibitory effect of
Ca2+-ATPase inhibition on renin secretion was reversed
within seconds by lowering of the extracellular calcium concentration
into the submicromolar range but was not affected by lanthanum,
gadolinium, flufenamic acid, or amlodipine. These data suggest that
calcium influx triggered by release of calcium from internal stores is a powerful mechanism to inhibit renin secretion from juxtaglomerular cells. The store-triggered calcium influx pathway in juxtaglomerular cells is apparently not sensitive to classic blockers of the
capacitative calcium entry pathway.
thapsigargin; cyclopiazonic acid; endoplasmatic
calcium-adenosinetriphosphatase; isolated perfused rat kidney
 |
INTRODUCTION |
IT HAS BEEN PROPOSED FOR
DECADES that calcium plays an unusual role in the control of
renin secretion from renal juxtaglomerular cells in the way that an
increase in the calcium concentration inhibits the exocytosis of renin,
whereas in other secretory cells calcium supports secretion. The
assumption of inhibitory effects on renin secretion is based on the
evidence that lowering of the extracellular concentration of calcium
stimulates renin secretion (1, 4,
9, 14, 24, 27,
29, 39) and that calcium-mobilizing hormones
inhibit renin secretion (9, 18,
27), dependent on the availability of extracellular
calcium (4, 24, 27, 29, 39). Whether it is the internal calcium
release or the transmembrane calcium influx that is relevant for the
control of renin secretion cannot be distinguished from previous
experiments because external calcium is required for both filling of
internal stores and for influx into the cytosol. Moreover, also the
routes along which calcium could enter juxtaglomerular cells, in
particular the role of voltage-gated calcium channels, are subject to
controversy (3, 7, 8,
12, 15, 17, 19,
23, 30). Although we could not find
electrophysiological evidence for a functional role of voltage-gated
calcium channels in renal juxtaglomerular cells (19), we
found that angiotensin II, which is a classic inhibitor of renin
secretion, mobilized calcium from internal stores and transiently
increased the calcium permeability of juxtaglomerular cells
(17). The nature of this angiotensin II-triggered calcium influx pathway and its relevance for renin secretion, however, is yet unknown.
During the last decade evidence has been elaborated that release of
calcium from internal stores can trigger transmembrane calcium influx
through a signal related to the filling state of internal calcium
stores (2, 26). The resulting
calcium-release-activated calcium current
(Icrac) flowing across the plasma membrane is detectable by using the patch-clamp technique (11). Such a
store-operated calcium influx is seen in a broad variety of cells
(25), but its existence in renal juxtaglomerular cells has
not been demonstrated till now. We therefore wondered whether such a
calcium store-regulated calcium influx also exists in renal
juxtaglomerular cells and what its impact for renin secretion may be.
Store-triggered calcium influx can experimentally be activated by
inhibition of calcium uptake into internal stores through the
inhibition of endoplasmatic Ca2+-ATPases (33,
34). We therefore characterized the effects of the
Ca2+-ATPase inhibitors thapsigargin and cyclopiazonic acid
on renin secretion from isolated perfused rat kidneys. Our results
indicate that store-triggered calcium influx acts as a powerful
inhibitor mechanism for renin secretion.
 |
MATERIALS AND METHODS |
Isolated perfused rat kidney.
Male Sprague-Dawley rats (280-330 g body wt), having free access
to commercial pellet chow and tap water, were obtained from the local
animal house and used throughout. Kidney perfusion was performed in a
recycling system (30). In brief, the animals were
anesthetized with 100 mg/kg of
5-ethyl-5-(1-methylbutyl)-2-thiobarbituric acid (Trapanal, Byk Gulden,
Konstanz, Germany). Volume loss during the preparation was substituted
by intermittent injections of physiological saline via a catheter
inserted into the jugular vein. After opening of the abdominal cavity
by a midline incision, the right kidney was exposed and placed in a
thermoregulated metal chamber. The right ureter was cannulated with a
small polypropylene tube (PP-10) that was connected to a larger
polyethylene catheter (PE-50). After intravenous heparin injection (2 U/g) the aorta was clamped distal to the right renal artery so that the
perfusion of the right kidney was not disturbed during the following
insertion of the perfusion cannula in the aorta distal to the clamp.
After ligation of the large vessels branching off the abdominal aorta, a double-barreled perfusion cannula was inserted into the abdominal aorta and placed close to the aortic clamp distal to the origin of the
right renal artery. After ligation of the aorta proximal to the right
renal artery, the aortic clamp was quickly removed and perfusion was
started in situ with an initial flow rate of 8 ml/min. By using this
technique, a significant ischemic period of the right kidney was
avoided. The right kidney was excised, and perfusion at constant
pressure (100 mmHg) was established. To this end the renal artery
pressure was monitored through the inner part of the perfusion cannula
(Statham Transducer P 10 EZ), and the pressure signal was used for
feedback control of a peristaltic pump. The perfusion circuit was
closed by draining the venous effluent via a metal cannula back into a
reservoir (200-220 ml). The basic perfusion medium, which was
taken from a thermostated (37°C) reservoir, consisted of a modified
Krebs-Henseleit solution containing (in mM) all physiological amino
acids in concentrations between 0.2 and 2.0 mM, 8.7 glucose, 0.3 pyruvate, 2.0 L-lactate, 1.0
-ketoglutarate, 1.0 L-malate, and 6.0 urea. The perfusate was supplemented with
6 g/100 ml bovine serum albumin, 1 mU/100 ml vasopressin 8-lysine, and
freshly washed human red blood cells (10% hematocrit). Ampicillin (3 mg/100 ml) and flucloxacillin (3 mg/100 ml) were added to inhibit
possible bacterial growth in the medium. To improve the functional
preservation of the preparation, the perfusate was continuously
dialyzed against a 25-fold volume of the same composition but lacking
erythrocytes and albumin. For oxygenation of the perfusion medium the
dialysate was gassed with a 94% O2-6% CO2
mixture. Under these conditions both glomerular filtration and
filtration fraction remain stable for at least 90 min at values of ~1
ml · min
1 · g
1 and 7%,
respectively (30). Perfusate flow rates were obtained from
the revolutions of the peristaltic pump, which was calibrated before
and after each experiment. Renal flow rate and perfusion pressure were
continuously monitored by a potentiometric recorder. After the
reperfusion loop perfusate flow was established, rates usually
stabilized within 15 min. Stock solutions of the drugs to be tested
were dissolved in freshly prepared perfusate and infused into the
arterial limb of the perfusion circuit directly before the kidneys at
3% of the rate of perfusate flow.
For determination of perfusate renin activity aliquots (~0.1 ml) were
drawn in intervals of 5 min from the arterial limb of the circulation
and the renal venous effluent, respectively. The samples were
centrifuged at 1,500 g for 15 min, and the supernatants were
stored at
20°C until assayed for renin activity. For determination of renin activity the perfusate samples were incubated for 1.5 h
at 37°C with plasma from bilaterally nephrectomized male rats as
renin substrate. The generated angiotensin I (ng · ml
1 · h
1) was determined by
radioimmunoassay (Sorin, Biomedica, Düsseldorf). Renin secretion
rates were calculated as the product of the arteriovenous differences
of renin activity and the perfusate flow rate (ml/min).
Five kidneys were used for each experimental protocol. Kidney weights
were 1.45 ± 0.18 g for the right kidney and 1.35 ± 0.16 g for the left kidney. As there were no significant
differences in the results when the data were related to the left or
the right kidney weight, all data in RESULTS are related on
the weight of the right kidney.
Chemicals.
Isoproterenol, thapsigargin, cyclopiazonic acid, gadolinium
(III)-chloride, lanthanum chloride, and flufenamic acid were purchased from Sigma Chemical (Deisenhofen, Germany).
For lowering calcium concentration into the submicromolar range, we
either added the calcium chelator EGTA (3.12 mM; Sigma Chemical) to the
perfusate or we used a nominally calcium-free dialysate.
Statistics.
For evaluation of significance of a certain experimental maneuver on
renin secretion, all renin secretion rates obtained within this
experimental period (4 values) were averaged and compared with the
average values of renin secretion of an adjoining experimental period.
Student's paired t-test was used to calculate levels of significance within individual kidneys. P < 0.05 was
considered significant.
 |
RESULTS |
Effects of Ca2+-ATPase inhibition on
renin secretion and perfusate flow.
Basal flow rates and renin secretion rates from the isolated rat
kidneys reached stable plateaus 10-15 min after onset of artificial perfusion (Fig. 1). To deplete
internal calcium stores we used the Ca2+-ATPase inhibitor
thapsigargin (300 nM). Thapsigargin produced a marked fall in renin
secretion (P < 0.01) (Fig. 1, bottom), whereas perfusate flow rates at constant pressure declined only moderately (not significant) (Fig. 1, top). Addition of
isoproterenol (10 nM) to the perfusate in the presence of thapsigargin
increased flow rates (not significant) (Fig. 1, top) and
restored basal renin secretion rates (Fig. 1, bottom). If
isoproterenol was administered in the absence of thapsigargin, renin
secretion increased eightfold over basal (P < 0.01)
(Fig. 1, bottom). Flow changes were not statistically
significant. Apparently, thapsigargin not only inhibited basal renin
secretion but also markedly attenuated the stimulability by
-adrenoreceptor activation.

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Fig. 1.
Effects of thapsigargin (300 nM) and isoproterenol
(isoprot; 10 nM) on renin secretion rate and perfusate flow ( ).
, Time control without thapsigargin. Values are
means ± SE.
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A similar attenuation of isoproterenol-stimulated renin secretion was
achieved with cyclopiazonic acid (20 µ M), another established endoplasmatic Ca2+-ATPase inhibitor, which inhibited renin
secretion also after a significant prestimulation with isoproterenol,
suggesting that inhibition of Ca2+-ATPase does not only
prevent stimulation of renin secretion but also reverses a stimulated
renin secretion (Fig. 2,
bottom). Again, perfusate flow was not altered significantly
by inhibition of the endoplasmatic Ca2+-ATPase (Fig. 2,
top).

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Fig. 2.
Effects of isoproterenol (10 nM) and cyclopiazonic acid
(20 µM) on perfusate flow and renin secretion rate. Values are
means ± SE. For statistics, see text.
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Similarly, stimulation of renin secretion two- to threefold by
inhibiting the macula densa salt transport with bumetanide (100 µM)
(P < 0.05 vs. control) or lowering the perfusion
pressure to 40 mmHg (P < 0.05 vs. control) was
reversed by adding thapsigargin (Fig. 3)
(P < 0.05 vs. stimulated values for bumetanide and
lowered pressure), indicating that the inhibitory action of
Ca2+-ATPase blockers is not restricted to a specific
pathway of stimulation of renin secretion. Perfusate flow did not
change significantly after either administration of bumetanide or
addition of thapsigargin. As expected, reduction of perfusion pressure
to 40 mmHg led to a significant decrease in perfusate flow.

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Fig. 3.
Effects of bumetanide (100 µM; ) or reduction
of perfusion pressure to 40 mmHg ( ) and thapsigargin
(300 nM) on perfusate flow and renin secretion rate. Values are
means ± SE. For statistics, see text.
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Relevance of extracellular calcium for the inhibitory effects of
Ca2+-ATPase inhibitors.
The next set of experiments was designed to evaluate the relevance of
extracellular calcium for the effects of Ca2+-ATPase
inhibitors on renin secretion. For this purpose renin secretion was
prestimulated by isoproterenol, which then was significantly attenuated
by thapsigargin (P < 0.05) (Fig.
4). In the presence of isoproterenol plus
thapsigargin, the concentration of extracellular calcium was then
rapidly lowered from 3 mM into the lower submicromolar range by the
addition of 3.12 mM EGTA to the perfusate. This maneuver almost
instantaneously reversed the inhibition of renin secretion by
thapsigargin (Fig. 4) and tended to increase perfusate flow (not
significant). The effect of EGTA was completely reversible, because,
after withdrawal of EGTA, renin secretion values rapidly fell to below
control (Fig. 4).

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Fig. 4.
Effects of lowering extracellular calcium by addition of
EGTA on the effects of thapsigargin. Stimulation of renin secretion
with isoproterenol (10 nM) and concomitant administration of
thapsigargin (300 nM). Extracellular calcium concentration was lowered
into the submicromolar range by adding EGTA (3.12 mM) to the perfusate
over a period of 10 min, following recovery period by stopping EGTA
infusion. Values are means ± SE. * P < 0.05.
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To confirm the calcium dependency of the inhibitory effects of
thapsigargin on renin secretion, we performed a similar set of
experiments as described above but used a different way of lowering the
calcium concentration in the perfusate. By switching from the standard
dialysate containing 3 mM calcium to a nominally calcium-free dialysate
the calcium concentration in the perfusate was lowered into the
submicromolar range. This procedure led to a significant increase in
perfusate flow and a moderate increase in renin secretion (Fig.
5). Addition of isoproterenol led
to a significant stimulation of renin secretion at low calcium
(
) as well as at normal extracellular calcium concentrations
(
). As seen in previous studies this increase was more
pronounced at low extracellular calcium concentrations compared with
the normal calcium concentration. Administration of thapsigargin in this situation suppressed renin secretion rate significantly at normal
calcium but failed to attenuate renin secretion under low-calcium conditions (Fig. 5).

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Fig. 5.
Effects of calcium-free perfusate on renin secretion and
flow rate and on the effects of isoproterenol (10 nM) and thapsigargin
(300 nM; ). , Time control with physiological
extracellular calcium concentrations and isoproterenol and thapsigargin
perfusion. Values are means ± SE. For statistics, see text.
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Effects of blockers of store-operated calcium channels and L-type
calcium channels on thapsigargin-induced inhibition of renin secretion.
Assuming that the inhibitory effect of Ca2+-ATPase blockade
on renin secretion was causally related to calcium influx from the extracellular space, we tested the effects of drugs that were previously reported to block store- operated calcium entry, such as
lanthanum, gadolinium, or flufenamic acid (13,
32). As shown in Fig. 6,
however, neither lanthanum nor flufenamic acid or gadolinium was
capable of reversing the inhibitory effect of thapsigargin on renin
secretion. Moreover, they exerted no significant effect on perfusate
flow. Also blocking L-type calcium channels by amlodipine (5 µM) had
no effect on the renin suppressing effects of thapsigargin (Fig. 6). In
contrast, lowering extracellular calcium into the submicromolar range
by adding EGTA (3.12 mM) led to an increase in renin secretion to
isoproterenol-stimulated values, indicating a reversal of the
thapsigargin effect (Fig. 6).

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Fig. 6.
Renin secretion rates as percent of values after isoproterenol
stimulation. Values are means ± SE. Effect of lanthanum (lant; 50 µM), flufenamic acid (flufen; 100 µM), gadolinium (gado; 50 µM),
amlodipine (amlo; 5 µM), and EGTA (3.12 mM) on renin secretion rate
and on thapsigargin (thap; 300 nM) effect on renin secretion. Iso,
isoproterenol (10 nM). n.s., Not significant. # P < 0.001 vs. isoproterenol alone.
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 |
DISCUSSION |
The purpose of our study was to examine the effect of calcium
influx triggered by depletion of internal stores on renin secretion from renal juxtaglomerular cells. To empty internal calcium stores we
used a widely accepted maneuver, namely, inhibition of calcium uptake
into internal stores via the inhibition of endoplasmatic Ca2+-ATPases by using thapsigargin and cyclopiazonic acid.
Both drugs have been shown to increase intracellular calcium
concentration primarily by inhibition of endoplasmatic
Ca2+-ATPase and thereby blocking the calcium transport from
the cytosol into the intracellular calcium stores. The resulting
calcium depletion of the stores activates a calcium influx from the
extracellular space via store-operated calcium channels
(6, 33, 34, 36, 37). The activation of store-operated calcium channels
seems restricted to stores sensitive to inositol triphosphate
(10), a known second messenger of angiotensin II.
Our data now show that inhibitors of Ca2+-ATPase in fact
are highly effective on renin secretion, in the way that they strongly inhibit basal and stimulated renin secretion. This inhibitory effect is
not restricted to a specific pathway of stimulation because it not only
affected renin secretion stimulated by
-adrenoreceptor activation
but also attenuated stimulation by inhibition of macula densa salt
transport with bumetanide and by a drop in the renal artery pressure.
This inhibitory effect of the Ca2+-ATPases was calcium
dependent because thapsigargin failed to suppress
isoproterenol-stimulated renin secretion when extracellular calcium
concentrations were low. In addition, lowering extracellular calcium
into the submicromolar range by adding EGTA immediately reversed
thapsigargin-induced renin suppression. Given a specific effect of the
Ca2+-ATPase inhibitors on renin secretion that is related
to calcium, then their effects on renin secretion could be due either
to an accumulation of cytosolic calcium, which cannot flow off into internal stores, or to an activation of calcium influx from outside, triggered by a signal related to the filling state of internal calcium
stores. The observation that the inhibitory action of Ca2+-ATPase inhibitors on renin secretion was almost
instantaneously abolished by a lowering of the extracellular calcium
concentration supports the conclusion that it is the calcium influx
from outside that primarily mediates the inhibitory action of
Ca2+- ATPase blockers on renin secretion.
We infer from these findings, that a significant store-operated calcium
influx exists in renal juxtaglomerular cells and that activation of
this influx represents a powerful inhibitory signal for renin
secretion. Both conclusions are in good accordance with previous
findings. Thus we have reported previously that angiotensin II
mobilizes calcium from internal stores in juxtaglomerular cells and
transiently increases the calcium permeability of the plasma membrane,
what would be compatible with store-regulated calcium influx
(17). Furthermore, it is well known that the inhibitory action of angiotensin II on renin secretion is strongly dependent on
extracellular calcium, compatible with an inhibition of renin secretion
by store-operated calcium influx (1, 39).
The results of our study, moreover, suggest that the store-regulated
calcium influx into renal juxtaglomerular cells does not follow the
well-characterized pathway of store-operated calcium influx, which can
be blocked by lanthanum, gadolinium, or flufenamic acid
(13, 28, 32). L-type calcium
channels do not appear to play a role in mediating the effects of
thapsigargin on the renin-secretion either, as amlodipine failed to
reverse its suppression mediated by thapsigargin. Alternative ways for
calcium influx include the recently identified more unspecific cation
channels that are also activated by depletion of internal calcium
stores (21, 38, 41) and
calcium-activated calcium channels that are store independent and have
been detected in a large variety of cells (16,
22, 40).
A further interesting result of our study is that the only moderate
attenuation of perfusate flow by thapsigargin and cyclopiazonic acid
indicating that inhibition of endoplasmatic reticulum
Ca2+-ATPase has only minor effects on the contractility of
renal resistance vessels in our experimental model. Although the renal
vascular resistance is set on a rather low level in the isolated
perfused kidney model compared with the in vivo situation and the
interpretation of the perfusate flow changes might therefore be
limited, it has been shown several times that vasoconstrictors like
angiotensin II mediate a dose-dependent vasoconstriction in our model
(30, 35). Therefore, it can be speculated
from our results that internal calcium stores and calcium
release-activated calcium channels are not the main regulatory step in
the control of vascular tone of renal resistance vessels. Our results
are in good accordance with a recent study showing thapsigargin not
altering diameters of afferent and efferent arterioles of isolated
perfused hydronephrotic kidneys under basal conditions
(35). Furthermore, our data support previous findings that
angiotensin II-induced calcium influx mediating vasoconstriction of
resistance vessels and suppression of renin secretion in
juxtaglomerular cells follows to different pathways. Although we and
others found a marked effect of L-type Ca2+-channel
blockers on regulation of vascular tone (5,
20, 30), we found no attenuation of renin
secretion (30). As mentioned above, we could not find
evidence for a role for voltage-operated calcium channels in
juxtaglomerular cells (19) but in more proximal smooth
muscle cells of afferent arterioles (31).
In conclusion, our data show a marked inhibitory effect on renin
secretion by inhibition of the endoplasmatic Ca2+-ATPase.
Instantaneous reversal of this inhibition by lowering extracellular
calcium concentration into the submicromolar range suggests that a
calcium influx from the extracellular space is responsible for this
inhibition. Store-operated calcium channels do not appear to be a main
regulatory step for the contractility of renal resistance vessels,
because inhibition of endoplasmatic Ca2+-ATPase attenuated
perfusate flow only slightly. Together, these results emphasize our
previous findings that calcium influx in juxtaglomerular cells and
renal smooth muscle cells mediating suppression of renin secretion and
vasoconstriction follow different pathways.
 |
ACKNOWLEDGEMENTS |
This study was financially supported by the Deutsche
Forschungsgemeinschaft (Ku 859/2-3).
 |
FOOTNOTES |
Address for reprint requests and other correspondence:
F. Schweda, Institut für Physiologie I, Universität
Regensburg, 93040 Regensburg, Germany (E-mail:
frank.schweda{at}klinik.uni-regensburg.de).
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 17 August 1999; accepted in final form 1 March 2000.
 |
REFERENCES |
1.
Antonipillai, I,
and
Horton R.
Role of extra- and intracellular calcium and calmodulin in renin release from rat kidney.
Endocrinology
117:
601-606,
1985[Abstract].
2.
Berridge, MJ.
Capacitative calcium entry.
Biochem J
312:
1-11,
1995[ISI][Medline].
3.
Churchill, PC,
and
Churchill MC.
Bay K 8644, a calcium channel agonist, inhibits renin secretion in vitro.
Arch Int Pharmacodyn Ther
285:
87-97,
1987[ISI][Medline].
4.
Churchill, PC,
and
Churchill MC.
Effects of trifluoperazine on renin secretion of rat kidney slices.
J Pharmacol Exp Ther
224:
68-72,
1983[Abstract].
5.
Cohen, AS,
and
Fray JSC
Calcium dependence of myogenic renal plasma flow autoregulation: evidence from the isolated perfused rat kidney.
J Physiol (Lond)
330:
449-460,
1982[Abstract].
6.
Demaurex, N,
Lew DP,
and
Krause KH.
Cyclopiazonic acid depletes intracellular calcium stores and activates an influx pathway for divalent cations in HL-60 cells.
J Biol Chem
267:
2318-2324,
1992[Abstract/Free Full Text].
7.
Dietz, JR.
Effects of a calcium channel agonist on renin release from perfused rat kidneys.
Ren Physiol
9:
279-286,
1986[ISI][Medline].
8.
Fray, JCS
Mechanism by which renin secretion from perfused rat kidneys is stimulated by isoprenaline and inhibited by high perfusion pressure.
J Physiol
308:
1-13,
1989[Abstract].
9.
Hackenthal, E,
Paul M,
Ganten D,
and
Taugner R.
Morphology, physiology and molecular biology of renin secretion.
Physiol Rev
70:
1067-1116,
1990[Free Full Text].
10.
Hoth, M,
and
Penner R.
Calcium release-activated calcium current in rat mast cells.
J Physiol (Lond)
465:
359-386,
1993[Abstract].
11.
Hoth, M,
and
Penner R.
Depletion of intracellular calcium stores activates a calcium current in mast cells.
Nature
355:
353-356,
1992[ISI][Medline].
12.
Ichihara, T,
Matsumura Y,
Shinyama H,
Ohyama T,
and
Morimoto S.
Effects of Bay K-8644 on renal function and renin secretion in anesthetized rats.
Life-Sci
44:
1945-1953,
1989.
13.
Jan, CR,
Ho CM,
Wu SN,
and
Tseng CJ.
Mechanism of rise and decay of thapsigargin-evoked calcium signals in MDCK cells.
Life Sci
64:
259-267,
1999[ISI][Medline].
14.
Jensen, BL,
and
Skott O.
Renin release from permeabilized juxtaglomerular cells is stimulated by chloride but not by low calcium.
Am J Physiol Renal Fluid Electrolyte Physiol
266:
F604-F611,
1994[Abstract/Free Full Text].
15.
Jones-Dombi, T,
and
Churchill P.
Bay K 8644 inhibits renin secretion in isolated perfused rat kidneys.
Life Sci
53:
1531-1537,
1993[ISI][Medline].
16.
Korbmacher, C,
Volk T,
Segal AS,
Boulpaep EL,
and
Fromter E.
A calcium-activated and nucleotide-sensitive nonselective cation channel in M-1 mouse cortical collecting duct cells.
J Membr Biol
146:
29-45,
1995[ISI][Medline].
17.
Kurtz, A,
and
Penner R.
Angiotensin II induces oscillations of intracellular calcium and blocks anomalous inward rectifying potassium current in mouse renal juxtaglomerular cells.
Proc Natl Acad Sci USA
86:
3423-3427,
1989[Abstract].
18.
Kurtz, A,
Pfeilschifter J,
Hutter A,
CBührle Nobiling R,
Taugner R,
Hackenthal R,
and
Bauer C.
Role of protein kinase C in the inhibition of renin release caused by vasoconstrictors.
Am J Physiol Cell Physiol
250:
C563-C571,
1986[Abstract/Free Full Text].
19.
Kurtz, A,
Skott O,
Chegini S,
and
Penner R.
Lack of evidence for a functional role of voltage-operated calcium channels in juxtaglomerular cells.
Pflügers Arch
416:
281-287,
1990[ISI][Medline].
20.
Loutzenhiser, R,
and
Epstein M.
Effects of calcium antagonists on renal hemodynamics.
Am J Physiol Renal Fluid Electrolyte Physiol
249:
F619-F629,
1985[ISI][Medline].
21.
Lückhoff, A,
and
Clapham DE.
Calcium channels activated by depletion of internal calcium stores in A431 cells.
Biophys J
67:
177-182,
1994[Abstract].
22.
Lückhoff, A,
and
Clapham DE.
Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca2+-permeable channel.
Nature
355:
356-358,
1992[ISI][Medline].
23.
Matsumura, Y,
Uriu T,
Shinyama H,
Sasaki Y,
and
Morimoto S.
Inhibitory effects of calcium channel agonists on renin release from rat kidney cortical slices.
J Pharmacol Exp Ther
241:
1000-1005,
1987[Abstract].
24.
Naftilan, AJ,
and
Oparil S.
The role of calcium in the control of renin release.
Hypertension
4:
670-675,
1982[Abstract].
25.
Parekh, AB,
and
Penner R.
Store depletion and calcium influx.
Physiol Rev
77:
901-930,
1997[Abstract/Free Full Text].
26.
Putney, JW.
Capacitative calcium entry revisited.
Cell Calcium
11:
611-624,
1990[ISI][Medline].
27.
Ritthaler, T,
Scholz H,
Ackermann M,
Riegger GAJ,
Kurtz A,
and
Krämer BK.
Effects of endothelins on renin secretion from isolated mouse renal juxtaglomerular cells.
Am J Physiol Renal Fluid Electrolyte Physiol
268:
F39-F45,
1995[Abstract/Free Full Text].
28.
Sarosi, GA,
Bernhart DC,
Turner DJ,
and
Mulholland MW.
Capacitative Ca2+ entry in enteric glia induced by thapsigargin and extracellular ATP.
Am J Physiol Gastrointest Liver Physiol
275:
G550-G555,
1998[Abstract/Free Full Text].
29.
Scholz, H,
Hamann M,
Götz KH,
and
Kurtz A.
Role of calcium ions in the pressure control of renin secretion from the kidneys.
Pflügers Arch
428:
173-178,
1994[ISI][Medline].
30.
Scholz, H,
and
Kurtz A.
Disparate effects of calcium channel blockers on pressure dependence of renin secretion and flow in the isolated perfused rat kidney.
Pflügers Arch
421:
155-162,
1992[ISI][Medline].
31.
Scholz, H,
and
Kurtz A.
Differential regulation of cytosolic calcium between afferent arteriolar smooth muscle cells from mouse kidney.
Pflügers Arch
431:
46-51,
1995[ISI][Medline].
32.
Schumann, S,
Greger R,
and
Leipziger J.
Flufenamate and Gd3+ inhibit stimulated Ca2+ influx in the epithelial cell line CFPAC-1.
Pflügers Arch
428:
583-589,
1994[ISI][Medline].
33.
Takemura, H,
Hughes AR,
Thastrup O,
and
Putney JW.
Activation of calcium entry by the tumor promotor thapsigargin in parotid acinar cells. Evidence that an intracellular calcium pool and not an inositol phosphate regulates calcium fluxes at the plasma membrane.
J Biol Chem
264:
12266-12271,
1989[Abstract/Free Full Text].
34.
Takemura, H,
and
Putney JW.
Capacitative calcium entry in parotid acinar cells.
Biochem J
258:
409-412,
1989[ISI][Medline].
35.
Takenaka, T,
Suzuki H,
Fujiwara K,
Kanno Y,
Ohno Y,
Hayashi K,
Nagahama T,
and
Saruta T.
Cellular mechanisms mediating rat renal microvascular constriction by angiotensin II.
J Clin Invest
100:
2107-2114,
1997[Abstract/Free Full Text].
36.
Thastrup, O,
Cullen PJ,
Drobak BK,
Hanley MR,
and
Dawson AP.
Thapsigargin, a tumor promotor, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmatic reticulum Ca2+-ATPase.
Proc Natl Acad Sci USA
87:
2466-2470,
1990[Abstract].
37.
Thastrup, O,
Dawson AP,
Scharff O,
Foder B,
Cullen PJ,
Drobak BK,
Bjerrum PJ,
Christensen SB,
and
Hanley MR.
Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage.
Agents Actions
27:
17-23,
1989[ISI][Medline].
38.
Vaca, L,
and
Kunze DL.
IP3-activated channels in the plasma membrane of cultured vascular endothelial cells.
Am J Physiol Cell Physiol
269:
C733-C738,
1995[Abstract].
39.
Vandongen, R,
and
Peart WS.
Calcium dependence of the inhibitory effect of angiotensin on renin secretion in the isolated perfused kidney of the rat.
Br J Pharmacol
50:
125-129,
1975[Medline].
40.
Von Tscharner, V,
Prod'hom B,
Baggiolini M,
and
Reuter H.
Ion channels in human neutrophils activated by a rise in free cytosolic calcium concentration.
Nature
324:
369-372,
1986[ISI][Medline].
41.
Worley, JF,
McIntyre MS,
Spencer B,
and
Duces ID.
Depletion of intracellular Ca2+ stores activates a maltotoxin-sensitive nonselective cationic current in beta-cells.
J Biol Chem
269:
32055-32058,
1994[Abstract/Free Full Text].
Am J Physiol Renal Fluid Electrolyte Physiol 279(1):F170-F176
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