1 European Institute for
Peptide Research, Gramicidin-perforated patch clamp experiments and
microfluorimetric measurements were performed to study the ionic
mechanisms involved in the
The intermediate lobe of the frog pituitary is a valuable model in
which to investigate the effect of regulatory substances. In contrast
to the rat pars intermedia, which contains two distinct cell types,
i.e., melanotrophs and corticotrophs, the frog pars intermedia is
composed of a homogeneous population of cells (37). In this respect,
the intermediate lobe of the frog pituitary offers the same advantages
as a cell line without the drawbacks of transformed tumoral cells. In
fact, amphibian melanotrophs have already been used to study the
mechanism of action of biologically active compounds (for review see
Ref. 37).
In a recent study, we have demonstrated that two highly specific
Animals.
Adult male frogs (Rana ridibunda; body
weight 30-40 g) were obtained from a commercial supplier
(Couétard, Saint-Hilaire de Riez, France). Frogs were housed in a
temperature-controlled room (8°C) under an established 12:12-h
light-dark photoperiod (lights on from 0600 to 1800). The animals had
free access to running water and were maintained under these conditions
for Reagents and test substances.
Leibovitz L-15 culture medium, protease (type IX), collagenase (type
IA), GTP, and gramicidin D were purchased from Sigma Chemical (St.
Louis, MO). HEPES was obtained from Research Organics (Cleveland, OH).
Cholera toxin (CTX) was from List Biological Laboratories (Campbell,
CA). Boehringer Mannheim (Mannheim, Germany) supplied kanamycin, the
antibiotic-antimycotic solution, fetal calf serum, and BSA (fraction
V). Indo 1 acetoxymethyl ester (indo 1-AM) was from Molecular Probes
(Eugene, OR). Tissue culture dishes were obtained from CML (Nemours,
France). (+)-Pentazocine and DTG were obtained from Jouveinal (Fresnes, France).
Cell culture for electrophysiological experiments.
Eight neurointermediate lobes (NIL) were dissected and washed in
Leibovitz L-15 culture medium adjusted to Rana
ridibunda osmolality and supplemented with
CaCl2 (0.1 g/l), glucose
(0.2 g/l), and 1% (vol/vol) of the kanamycin and
antimycotic-antibiotic solution. The tissues were enzymatically
dissociated in the same medium, containing 0.15% protease and
0.15% collagenase, for 15 min at 22°C. After mechanical
dispersion, the cells were centrifuged (50 g) for 15 min, rinsed three times,
and suspended in Leibovitz medium supplemented with 10%
heat-inactivated fetal calf serum and antibiotics. The cells were then
plated at a density of 10,000 cells per 35-mm tissue culture dish.
Cultured cells were incubated at 24°C in a humid atmosphere
and used 5-10 days after plating.
Cell culture for intracellular calcium measurements.
NIL (10 per culture) were collected in
Ca2+-free Ringer solution (in mM:
15 HEPES, 112 NaCl, 2 KCl, and 1 EGTA) supplemented with glucose (2 mg/ml), BSA (0.3 mg/ml), and 1% each of the kanamycin and
antibiotic-antimycotic solutions. The Ringer solution was gassed for 15 min with
O2-CO2
(95:5, vol/vol) before the experiment, and pH was adjusted to 7.4 with
NaOH. NIL were enzymatically dispersed at 24°C for 20 min with a
solution of collagenase (1.5 mg/ml) in a
Ca2+-free Ringer solution.
Nondissociated neural lobes were allowed to settle down, and the
supernatant, containing mainly dispersed melanotrophs, was sampled. The
cell suspension was sampled and then centrifuged three times (30 g; 5 min) with the
Ca2+-free Ringer solution.
Dissociated cells were resuspended in the L-15 solution already
described. Cells were then dispersed and plated on
poly-L-lysine-coated coverslips
and recovered with L-15 culture medium supplemented with 10% fetal
bovine serum. Microfluorimetric measurements were performed on 3- to
5-day-old cultured cells.
Electrophysiological procedures.
Electrophysiological recordings were performed at room temperature on
5- to 10-day-old cultured frog melanotrophs by use of the perforated
patch-clamp variation of the whole cell variation (33, 36). External
solutions used to perform the different experiments are detailed in
Table 1. Soft glass patch electrodes (microhematocrit tubes) were made on a vertical pipette puller (List
Electronic, Darmstadt, Germany), and the tip of the electrode was
polished with a microforge (Narishige, Tokyo, Japan) to achieve a final
resistance ranging from 3 to 5 M
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
-receptor-mediated stimulation of frog
(Rana ridibunda) pituitary
melanotrophs. The
-ligand (+)-pentazocine (50 µM) depressed a
sustained outward K+ current. The
kinetic properties of this K+
component, investigated by analyzing tail currents, were reminiscent of
those of the M current
(IM), with an
activation threshold close to
60 mV, a
21-mV half-maximal
activation potential, and two-component exponential deactivation
kinetics at
90 mV. (+)-Pentazocine (20 µM) produced
a 12-mV rightward shift of the activation curve and accelerated the
deactivation rate of the tail current. It is also demonstrated that
(+)-pentazocine (20 µM) reversibly increased both voltage-dependent
calcium conductances and internal calcium level. Altogether, these
results suggest that the
-receptor-induced modulation of
IM and calcium
currents likely underlies the increase of intracellular
[Ca2+].
-receptors; calcium channels; patch-clamp technique; melanotrophs; (+)-pentazocine
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
-RECEPTORS were first described as a new type of
opioid receptor mediating the psychotomimetic effects produced by
N-allylnormetazocine [(+/
)-SKF 10047] and related benzomorphans (27).
Subsequent studies have demonstrated that
-receptors represent a new
class of binding sites distinct from opioid receptors. In particular, the nonselective opioid antagonist naloxone does not block the in vivo
and in vitro effects of
-ligands (39). Furthermore,
-receptors
are enantioselective for the (+)-isomers of opioid agonists, whereas
opioid receptors are selective for the (
)-isomers (19). Although
two
-receptors, namely
1-
and
2-receptors, have been
pharmacologically described (31), several lines of evidence suggest the
existence of multiple types of
-receptors (3, 40). Recently, a
subclass of the
-receptor corresponding to a 27-kDa protein has been
cloned in the guinea pig and in humans (15, 18, 21). The function of
this protein remains largely unclear.
-Receptors are widely represented in various regions of the central
nervous system, including the cerebral cortex, hippocampus, striatum,
and cerebellum (12, 17). The presence of
-receptors has also been
demonstrated in the hypothalamus and pituitary (17), suggesting that
-receptors regulate hypothalamopituitary functions. In support of
this, it has been shown that various
-ligands enhance the secretion
of prolactin and corticosterone in rats (14). It has also been reported
that in vivo administration of
-antagonists causes a reduction of
the plasma concentration of
-melanocyte-stimulating hormone in the
rat (10). Although
-ligands have been shown to mediate a large array
of biological effects in central nervous, endocrine, and immune systems
(18, 20, 34, 35, 40), so far the cellular transduction mechanisms
associated with
-receptors are still poorly understood.
-receptor ligands, 1,2-ditolylguanidine (DTG) and (+)-pentazocine, stimulate the electrical activity of cultured frog melanotrophs through
the inhibition of both a voltage-activated
K+ conductance, i.e., the
delayed rectifier
[IK(V)],
and a yet-to-be-identified outward leak potassium current (33).
The aim of the present study was to further elucidate the ionic
mechanisms involved in the
-ligand-induced stimulation of the
electrical activity in pituitary cells. It is concluded that
-receptor activation stimulates voltage-gated calcium
conductances both directly and through a depolarizing process involving
the M current
(IM).
METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
1 wk before use. Animal manipulations were performed according to the recommendations of the French Ethical Committee and under the
supervision of authorized investigators.
after electrodes were filled with
the internal solution. Perforated patch-clamp experiments were
performed with gramicidin D (2), which was first dissolved in methanol
to a concentration of 10 mg/ml and then diluted in the pipette solution
to a final concentration of 100 µg/ml just before use. The
composition of the internal pipette solution used for recordings of
potassium currents was (in mM) 100 KCl and 10 HEPES (pH adjusted to 7.4 with KOH). Barium currents were obtained with an internal solution
composed (in mM) of 100 CsCl and 10 HEPES (pH adjusted to 7.4 with
CsOH). A short tip-filling (2 s) of each glass electrode with an
antibiotic-free internal solution was necessary just before the final
back-filling with the gramicidin-containing medium. The series
resistance achieved a stable value (4-15 M
) after 7-15 min
after the giga-seal formation. In whole cell experiments, GTP (100 µM) and EGTA (10 mM) were added in the internal pipette solution. The
series resistance was compensated at a value higher than 60% for all
recorded cells. Electric signals were amplified with an Axopatch 200A
amplifier (Axon Instruments, Foster City, CA) and acquired on an
IBM-compatible personal computer with a DIGIDATA 1200 interface and
pCLAMP 6.02 software (Axon Instruments). Potassium currents were
recorded at a 2-kHz sampling frequency and filtered at 1 kHz. Calcium
currents were sampled at 5.2 kHz and filtered at 2 kHz. All
voltage-activated currents were obtained after appropriate leak
correction using P/4 protocol.
Table 1.
Composition of external solutions used in electrophysiological
experiments
Calcium measurements.
Cultured cells were incubated at 24°C in the Ringer solution,
supplemented with glucose (2 mg/ml) and BSA (0.3 mg/ml) and containing
5 µM of the fluorescent probe indo 1-AM, for 30 min in the dark. At
the end of the incubation period, cells were washed with 2 ml of fresh
medium and placed on the stage of a Nikon Diaphot inverted microscope
(Tokyo, Japan) equipped for epifluorescence with an oil-immersion
objective (*100 CF Fluor series; numerical aperture, 1.3). The
variations of internal Ca2+ were
monitored by a dual-emission microfluorimeter system. The fluorescence
emission of indo 1-AM induced by excitation at 355 nm (Xenon lamp) was
recorded at two wavelengths (405 nm, corresponding to the
Ca2+-complexed form, and 480 nm,
corresponding to the free form) by separate photometers (P1, Nikon).
The 405-to-480-nm ratio (R, 405/480) was determined by using an
analogical divider (constructed by B. Dufy, Bordeaux, France) after
conversion of single photon currents to voltage signals. All three
signals (405 nm, 480 nm, and 405/480) were continuously recorded with a
three-channel voltage recorder (BD 100/101, Kipp & Zonen, Delft, The
Netherlands). The intracellular calcium concentration was calculated
according to the formula established by Grynkiewicz et al. (13):
[Ca2+]i = Kd × (R
Rmin)/(Rmax
R), where Rmin represents
the minimum fluorescence ratio obtained after incubation of cells in
Ringer solution containing 10 mM EGTA and 10 µM ionomycin,
Rmax is the maximum fluorescence
ratio obtained after incubation of cells in Ringer solution containing
10 mM CaCl2 and 10 µM ionomycin, and
is the ratio of fluorescence yields from the
Ca2+min/Ca2+max
indicator at 480 nm. The values for
Rmin,
Rmax, and
were 0.164, 1.82, and 1.62, respectively. The dissociation constant (Kd) for indo 1 (250 nM) has been previously determined (28).
Drug application.
(+)-Pentazocine was added to the external solution and sonicated for
20-30 s. DTG was first dissolved in ethanol (final concentration of ethanol <1% vol/vol) and mixed to the external solution.
-Ligand solutions were administered in the vicinity of the cell
under study by a pressure ejection system (76 mmHg) from a glass
pipette placed at a distance of 100-150 µm from the cell. The
bathing medium was continuously renewed with fresh external solution at a flow rate of 3 ml/min via a gravity-fed system. The excess of bathing
solution was continuously aspirated via a suction needle.
Analysis of currents. Current amplitudes were determined with the pCLAMP 6.02 analysis software (Clampfit). Exponential fits of the decaying phase of tail currents (calculated by the Simplex method) were also performed with Clampfit. Current-voltage (I/V) relationships were fitted by using Origin analysis software (Micrococal). Statistical comparisons were performed with the Student's paired or independent t-test and the Mann-Whitney or Wilcoxon test, depending on the experimental conditions. Quantitative data are expressed as means ± SE.
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RESULTS |
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The effects of (+)-pentazocine on frog pituitary melanotrophs were studied by use of the patch-clamp and microfluorimetry techniques in a total of 79 cells.
Electrophysiological recordings were performed using the gramicidin D-perforated patch variation of the standard whole cell approach (36) to avoid dialysis of intracellular messengers, which is inherent in the whole cell configuration.
Isolation of the sustained outward
K+ current.
In cells bathed in a low K+ and a
Ca2+- and
Na+-free external solution (Table
1), long-lasting depolarizing pulses (10 s) from 90 to 50 mV
elicited fast inactivating outward
K+ currents prolonged by a
sustained component (n = 8). The
1-agonist (+)-pentazocine (50 µM) markedly inhibited both the fast inactivating and the sustained
currents (Fig. 1). Whereas the
-ligand-induced reduction of the transient component is attributable
to the inhibition of the delayed rectifier outward
K+ current (33), the nature of the
sustained current altered by
-ligands remained to be identified
(33). To further characterize the properties of this latter component,
open-state relaxation experiments were performed. The low
K+ external solution was replaced
by a high K+ solution (20 mM;
Table 1). Under these conditions, reversal potential of
K+ ions was shifted from
98
to
40 mV. Consequently, a tail current was observed at the end
of a 10-s depolarizing step pulse because of the sudden increase in
driving force of K+ ions
(n = 13). The tail current occurring
at
90 mV represents the deactivation of the sustained component
(Fig. 2, A
and B). In addition, to avoid
calcium and calcium-dependent K+
currents, Mg2+ was substituted for
Ca2+ (Table 1).
|
|
Properties of the sustained outward
K+ current.
Melanotrophs were clamped at 90 mV and depolarized to potentials
between 50 and
90 mV by 20-mV steps (Fig.
2A). At depolarizing potentials
ranging from
30 to 50 mV, the evoked currents presented fast
activating and inactivating phases, followed by a sustained component.
By contrast, at potentials ranging between
50 and
90 mV,
only very weak inward currents were observed (Fig.
2A). As a consequence, the reversal
potential could be estimated at a value that corresponds to the
equilibrium potential of K+ ions
in the present experimental conditions
(EK =
40
mV). At the end of the depolarizing pulses, transient inward
deactivating currents were detected (Fig. 2,
A and
B). The tail current increased with
the depolarization in a sigmoid manner. The corresponding I/V plot obtained from seven
melanotrophs fitted well with a Boltzmann function (Fig.
2C; Table
2). The deactivation rate of the tail currents recorded after depolarizations to 50 mV was fitted by a
two-component exponential function, revealing the presence of a fast
(
1) and a slow
(
2) component in the current
decay (Fig. 2D; Table 2).
|
Effects of (+)-pentazocine on the
kinetic properties of the sustained outward
K+ current.
Melanotrophs were held at 90 mV, pulsed to a series of 10-s
depolarizing steps from 50 to 70 mV, and then returned to
90 mV. This experimental protocol was applied to each studied
cell in the absence and presence of (+)-pentazocine (20 µM).
(+)-Pentazocine significantly reduced the tail currents
(P < 0.05; Mann and Whitney) elicited after depolarizations positive to
50 mV (Fig.
3). Furthermore, (+)-pentazocine provoked a
pronounced shift of the voltage-dependent activation curve toward more
depolarized potentials (Fig. 3B; Table
2). The decrease in current amplitude was accompanied by an
acceleration of the deactivating phase, yielding a significant diminution of both time constants (P < 0.01 and P < 0.05 for
1 and
2, respectively; paired
t-test) deduced from the
double-exponential fit of the tail current elicited after a 50-mV
depolarizing step (Fig. 3A;
Table 2).
|
Effects of (+)-pentazocine on the
cytosolic calcium level.
The effects of -ligands on the intracellular calcium concentration
([Ca2+]i)
were studied by use of microfluorimetric measurements. Basal [Ca2+]i
was 18.8 ± 1.1 nM. Melanotrophs were challenged with
(+)-pentazocine or DTG (20 µM each) after periods of 2-3 min of
control recording to ensure that the tested cells did not present any
spontaneous oscillatory activity. Application of (+)-pentazocine (or
DTG; not shown) in the vicinity of the cells significantly elevated [Ca2+]i
(68.7 ± 6.4 nM, n = 29, P < 0.001; paired
t-test; Fig.
4). The response appeared within 5-25
s after the onset of the
-ligand application and gradually developed
to reach its maximum in a period of 46.2 ± 8.5 s
(n = 29).
|
Effects of (+)-pentazocine on
voltage-activated barium currents.
The effects of (+)-pentazocine (20 µM) were tested on a sample of 12 melanotrophs bathed in the
BaCl2-tetraethylammonium-TTX external solution (Table 1). Depolarizing step pulses from 80 to
0 mV elicited slowly inactivating inward barium currents
(IBa). Application of (+)-pentazocine gave rise to a significant
(P < 0.01; paired
t-test) and reversible augmentation of
IBa (Fig. 5, A and
B). The maximum increase in current
amplitude was recorded between 20 and 120 s after the application of
(+)-pentazocine (Fig. 5C).
Depolarizing ramps from
80 to 60 mV evoked bell-shaped inward
currents. (+)-Pentazocine clearly augmented the current amplitude for
potentials ranging from
50 to 30 mV (Fig.
5D).
|
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DISCUSSION |
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---|
A recent study has demonstrated that -ligands exert a positive
control on the electrical activity of frog melanotrophs by inhibiting a
voltage-dependent potassium current, namely
IK(V), and a leak
potassium current, both through a G protein-dependent pathway (33). The
aim of the present investigations was to determine other targets that
are controlled by
-receptors. Herein we have characterized, in frog
melanotrophs, an M-like current that is inhibited by
-ligands. In
addition, it is demonstrated for the first time that (+)-pentazocine, a
highly specific and selective
1-receptor ligand (4, 30),
stimulates voltage-dependent calcium conductances.
We have demonstrated that, in addition to the stimulation of the
electrical activity previously described in melanotrophs (33),
(+)-pentazocine induces a transient increase of
[Ca2+]i.
Several lines of evidence have suggested that, in spontaneously active
cells, calcium influx is triggered by sodium-dependent action
potentials through the activation of voltage-dependent calcium channels
occurring during the transient depolarizations (9, 24, 29). Moreover,
it has recently been proposed that slight variations in the discharge
frequency of action potentials were responsible for spontaneous
cytosolic calcium spiking activity in Xenopus
laevis melanotrophs (38). As a consequence, it is likely that in frog melanotrophs the -ligand-induced increase of
[Ca2+]i
is due, at least in part, to the inhibition of
IK(V), giving rise to a stimulation of an action potential discharge (33).
However, the modulation of electrical activity by -ligands has also
been attributed to variations of resting potential (33). As a result,
the observed
-ligand-induced depolarizations were identified as the
consequence of the clamping of a yet-to-be-identified tonic outward
potassium current (33). Because the properties of such a tonic
conductance were unknown in melanotrophs, we next undertook its kinetic
characterization. In conditions where calcium and sodium currents were
eliminated, a noninactivating potassium current was isolated. The
voltage-dependent properties of this conductance revealed an activation
threshold close to
60 mV, a half-maximal activation
potential between
20 and
25 mV, and a nearly
complete activation between 0 and 10 mV. All these characteristics fit
very well those of the M current previously described in neurons (6, 7)
and endocrine cells (32). In addition, it was found that this current
exponentially deactivates at hyperpolarized potential with fast and
slow time constants. This finding is consistent with other analyses of
M currents in rat lactotrophs (32) and bullfrog sympathetic neurons
(26). The values of the time constants in frog melanotrophs are in the
same range as those obtained in bullfrog sympathetic neurons but are
lower than in rat lactotrophs.
M current has been described in various neurons (1, 22, 25,
26) and recently in endocrine cells (32). Because
IM is one of the only sustained currents at rest in each cell
type, it appears as a major element in the control of membrane
excitability. Again, its properties in melanotrophs strongly suggest
that it contributes to the regulation of resting potential
[48 mV (23, 33)] and excitability. Another original
finding provided by the present investigations is that
IM is under the
control of
-receptors in endocrine cells. It is shown that
(+)-pentazocine dramatically shifted the activation curve toward more
positive potentials, resulting in a diminution of the net outward
potassium flux. Consequently, the
-ligand-mediated inhibition of
IM described in
this study likely participates in the previously reported inward potassium current provoked by DTG and (+)-pentazocine at potentials positive to
60 mV (33). The removal of the hyperpolarizing influence of IM
at rest as well as at interspike potentials would lead to an increased
excitability and to the observed
-ligand-induced depolarization
(33). This is strongly correlated with the increase in membrane
resistance occurring during the
-ligand-induced membrane depolarization (33). Together with the depression of
IK(V) (33), the
inhibition of IM
by
-ligands would have a critical role in the augmentation of
calcium influx by making cells more likely to fire action potentials
(25) and by further stimulating voltage-dependent calcium channels
(38).
Although our results strongly suggest that -ligands indirectly
activate calcium channels through the inhibition of potassium currents,
the possibility of an intracellular modulation of calcium channels by
-receptors was investigated. It is shown here for the first time
that (+)-pentazocine potentiates voltage-activated calcium
conductances. This observation markedly differs from other data
previously reported, demonstrating the depression of calcium influx in
rat forebrain synaptosomes (5) and in mouse hippocampal pyramidal
neurons (8). However, in this latter case, the high concentrations of
tested compounds clearly acted as open channel blockers, independent of
any
-receptor-mediated effect. In addition, it cannot be excluded
that in rat synaptosomes, the observed decrease in calcium influx
ascribed to the inhibition of calcium conductances would be the
consequence of an external blockade of the channels as well (8).
In our paradigm, the -ligand-induced augmentation of calcium current
developed gradually in contrast to the fast stimulating effect observed
on membrane potential and action potential firing (33). In very much
the same way as the increase in calcium current, the maximum
augmentation of cytosolic calcium level was observed after a relatively
long period after the application of the
-ligand. It is then
tempting to speculate that the early phase of calcium influx depends
mainly on the voltage-dependent modulation of calcium channels through
-receptor-mediated closing of
K+ conductances. In contrast, the
late peak calcium influx is more likely supported by an intracellular
pathway coupling
-receptors to calcium channels. The question of
whether stored calcium from the internal pools also contributes to the
increase of
[Ca2+]i
by
-ligands remains open. However, evidence has already been provided that inositol trisphosphate-triggered release of internal calcium provokes rapid and often sustained elevation of
[Ca2+]i
(11, 16), suggesting that the
[Ca2+]i
stores are not altered by the activation of
-receptors.
In conclusion, it appears that, in pituitary melanotrophs,
-receptors exert a complex regulation of membrane excitability through the inhibition of voltage-activated potassium conductances (33), including the newly characterized
IM. In addition,
it is demonstrated, for the first time to our knowledge, that
-ligands stimulate voltage-activated calcium conductances
independently of the K+ channel
pathway. Altogether, these results suggest that
-receptors modulate
cytosolic calcium level and subsequently control hormone release. In
addition, this work shows that frog melanotrophs constitute a model of
choice to further determine the intracellular messengers involved in
-ligand-induced responses.
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ACKNOWLEDGEMENTS |
---|
We thank Catherine Buquet for excellent technical assistance.
![]() |
FOOTNOTES |
---|
This work was supported by grants from INSERM (U 413), the Institut de Recherche Jouveinal, the European Union (Human Capital and Mobility Programme; ERBCHRXCT920017), and the Conseil Régional de Haute-Normandie. 0. Soriani was the recipient of a scholarship from the Fonds de la Recherche et de la Technologie (Cifre program).
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.
Address for reprint requests: L. Cazin, European Institute for Peptide Research (IFRMP No. 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, UA CNRS, Univ. of Rouen, 76821 MontSaintAignan, France.
Received 25 January 1999; accepted in final form 2 April 1999.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Adams, P. R.,
D. A. Brown,
and
A. Constanti.
Pharmacological inhibition of the M-current.
J. Physiol. Paris
332:
223-262,
1982.
2.
Akaike, N.
Gramicidin perforated patch recording and intracellular chloride activity in excitable cells.
Prog. Biophys. Mol. Biol.
65:
251-264,
1997.
3.
Bergeron, R.,
and
G. Debonnel.
Effects of low and high doses of selective sigma ligands: further evidence suggesting the existence of different subtypes of sigma receptors.
Psychopharmacology
129:
215-224,
1997[Medline].
4.
Bowen, W. D.,
B. R. De Costa,
S. B. Hellewell,
M. J. Walker,
and
K. C. Rice.
[3H](+)pentazocine: a potent and highly selective benzomorphan-based probe for sigma-1 receptors.
Mol. Neuropharmacol.
3:
117-126,
1990.
5.
Brent, P. J.,
L. Herd,
H. Saunders,
A. T. R. Sim,
and
P. R. Dunkley.
Protein phosphorylation and calcium uptake into rat forebrain synaptosomes: modulation by the sigma ligand, 1,3-ditolylguanidine.
J. Neurochem.
68:
2201-2211,
1997[Medline].
6.
Brown, D. A.,
and
P. R. Adams.
Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neuron.
Nature
283:
673-676,
1980[Medline].
7.
Brown, D. A.,
and
P. R. Adams.
M-Currents: an update.
Trends Neurosci.
11:
294-299,
1988[Medline].
8.
Church, J.,
and
E. J. Fletcher.
Blockade by sigma site ligands of high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones.
Br. J. Pharmacol.
116:
2801-2810,
1995[Abstract].
9.
Corcuff, J. B.,
N. C. Guérineau,
P. Mariot,
B. T. Lussier,
and
P. Mollard.
Multiple cytosolic calcium signals and membrane electrical events evoked in single arginine vasopressin-stimulated corticotrophs.
J. Biol. Chem.
374:
421-424,
1993.
10.
Eaton, M. J.,
K. J. Lookingland,
and
K. E. Moore.
The sigma receptor ligand rimcazole alters secretion of prolactin and alpha-melanocyte stimulating hormone by dopaminergic and non-dopaminergic mechanisms.
Eur. J. Pharmacol.
299:
171-177,
1996[Medline].
11.
Galas, L.,
M. Lamacz,
M. Garnier,
E. W. Roubos,
M.-C. Tono,
and
H. Vaudry.
Involvement of extracellular and intracellular calcium sources in TRH-induced -MSH secretion from frog melanotrope cells.
Mol. Cell. Endocrinol.
138:
25-39,
1998[Medline].
12.
Gonzalez-Alvear, G. M.,
D. Thompson-Montgomery,
S. E. Deben,
and
L. L. Werling.
Functional and binding properties of sigma receptors in rat cerebellum.
J. Neurochem.
65:
2509-2516,
1995[Medline].
13.
Grynkiewicz, G.,
M. Poenie,
and
R. Y. Tsien.
A new generation of Ca2+ indicators with greatly improved fluorescence properties.
J. Biol. Chem.
260:
3440-3450,
1985[Abstract].
14.
Gudelsky, G. A.,
and
J. F. Nash.
Neuroendocrinological and neurochemical effects of sigma ligands.
Neuropharmacology
31:
157-162,
1992[Medline].
15.
Hanner, M.,
F. F. Moebius,
A. Flandorfer,
H. G. Knaus,
J. Striessnig,
E. Kempner,
and
H. Glossmann.
Purification, molecular cloning, and expression of the mammalian sigma(1)-binding site.
Proc. Natl. Acad. Sci. USA
93:
8072-8077,
1996
16.
Hinkle, P. M.,
E. J. Nelson,
and
R. Ashworth.
Characterization of the calcium response to thyrotropin-releasing hormone in lactotrophs and GH cells.
Trends Endocrinol. Metabol.
7:
370-374,
1996.
17.
Jansen, K. L. R.,
R. L. M. Faull,
M. Dragunow,
and
R. A. Leslie.
Autoradiographic distribution of sigma receptors in human neocortex, hippocampus, basal ganglia, cerebellum, pineal and pituitary glands.
Brain Res.
559:
172-177,
1991[Medline].
18.
Jbilo, O.,
H. Vidal,
R. Paul,
N. De Nys,
M. Bensaid,
S. Silve,
P. Carayon,
D. Davi,
S. Galiegue,
B. Bourrié,
J.-C. Guillemot,
P. Ferrara,
G. Loison,
J.-P. Maffrand,
G. Le Fur,
and
P. Casellas.
Purification and characterization of the human Sr 31747A-binding protein.
J. Biol. Chem.
43:
27107-27115,
1997.
19.
Katz, J. L.,
R. D. Spealman,
and
R. D. Clark.
Stereoselective behavioral effects of N-allylnormetazocine in pigeons and squirrel monkeys.
J. Pharmacol. Exp. Ther.
232:
452-461,
1985[Abstract].
20.
Keats, A. S.,
and
J. Telford.
Narcotic antagonists as analgesics.
Adv. Chem. Ser.
45:
170-176,
1964.
21.
Kekuda, R.,
P. D. Prasad,
Y. J. Fei,
F. H. Leibach,
and
V. Ganapathy.
Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1).
Biochem. Biophys. Res. Commun.
229:
553-558,
1996[Medline].
22.
Kennedy, C.,
and
G. Henderson.
Inhibition of potassium currents by the sigma receptor ligand (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine in sympathetic neurons of the mouse isolated hypogastric ganglion.
Neuroscience
3:
725-733,
1990.
23.
Le Foll, F.,
E. Louiset,
H. Castel,
H. Vaudry,
and
L. Cazin.
Electrophysiological effects of various neuroactive steroids on the GABAA receptor in pituitary melanotrope cells.
Eur. J. Pharmacol.
331:
303-311,
1997[Medline].
24.
Louiset, E.,
L. Cazin,
M. Lamacz,
M. C. Tonon,
and
H. Vaudry.
Patch-clamp study of the ionic currents underlying action potentials in cultured frog pituitary melanotrophs.
J. Neuroendocrinol.
48:
507-515,
1988.
25.
Marrion, N. V.
Control of M-current.
Annu. Rev. Physiol.
59:
483-504,
1997[Medline].
26.
Marrion, N. V.,
P. R. Adams,
and
W. Gruner.
Multiple kinetic states underlying macroscopic M-currents in bullfrog sympathetic neurons.
Proc. R. Soc. Lond. (Biol.)
248:
207-214,
1992[Medline].
27.
Martin, W. R.,
C. E. Eades,
J. A. Thompson,
and
R. E. Huppler.
The effects of morphine- and nalomorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog.
J. Pharmacol. Exp. Ther.
197:
517-532,
1976[Abstract].
28.
Mollard, P.,
N. Guérineau,
J. Audin,
and
B. Dufy.
Measurements of Ca2+ transients using simultaneous dual-emission microspectrofluorimetry and electrophysiology in individual pituitary cells.
Biochem. Biophys. Res. Commun.
164:
1045-1054,
1989[Medline].
29.
Mollard, P.,
J.-M. Theler,
N. Guérineau,
P. Vacher,
C. Chiavaroli,
and
W. Schlegel.
Cytosolique Ca2+ of excitable pituitary cells at resting potentials is controlled by steady-state Ca2+ currents sensitive to dihydropyridines.
J. Biol. Chem.
269:
158-164,
1994.
30.
Monnet, F. P.,
B. R. De Costa,
and
W. D. Bowen.
Differentiation of sigma ligand-activated receptor subtypes that modulate NMDA-evoked [H-3]-noradrenaline release in rat hippocampal slices.
Br. J. Pharmacol.
119:
65-72,
1996[Abstract].
31.
Quirion, R.,
W. D. Bowen,
Y. Itzhak,
J. L. Junien,
J. M. Musacchio,
R. B. Rothman,
T. P. Su,
S. W. Tam,
and
D. P. Taylor.
A proposal for the classification of sigma-binding sites.
Trends Pharmacol. Sci.
13:
85-86,
1992[Medline].
32.
Sankaranarayanan, S.,
and
S. M. Simasko.
Characterization of an M-like current modulated by thyrotropin-releasing hormone in normal rat lactotrophs.
J. Neurosci.
16:
1668-1678,
1996[Abstract].
33.
Soriani, O.,
H. Vaudry,
Y. A. Mei,
F. J. Roman,
and
L. Cazin.
Sigma ligands stimulate the electrical activity of frog pituitary melanotrope cells through a G-protein-dependent inhibition of potassium conductances.
J. Pharmacol. Exp. Ther.
286:
163-171,
1998
34.
Su, T. P.
-Receptors: putative links between nervous, endocrine and immune systems.
Eur. J. Biochem.
200:
633-642,
1991[Abstract].
35.
Su, T. P.,
E. D. London,
and
J. H. Jaffe.
Steroid binding at sigma receptors suggests a link between endocrine, nervous and immune systems.
Science
240:
219-221,
1988[Medline].
36.
Tajima, Y.,
K. Ono,
and
N. Akaike.
Perforated patch-clamp recording in cardiac myocytes using cation-selective ionophore gramicidin.
Am. J. Physiol.
271 (Cell Physiol. 40):
C524-C532,
1996
37.
Tonon, M. C.,
L. Desrues,
M. Lamacz,
N. Chartrel,
B. G. Jenks,
and
H. Vaudry.
Multihormonal regulation of pituitary melanotrophs.
In: The Melanotropic Peptides, edited by H. Vaudry,
and A. N. Eberle. New York: New York Acad. Sci., 1993, p. 175-187.
38.
Valentijn, J. A.,
and
K. Valentijn.
Two distinct Na+ currents control cytosolic Ca2+ pulsing in Xenopus leavis pituitary melanotrophs.
Cell Calcium
21:
241-251,
1997[Medline].
39.
Vaupel, D. B.
Naltrexone fails to antagonize the effects of PCP and SKF 10047 in the dog.
Eur. J. Pharmacol.
92:
269-274,
1983[Medline].
40.
Walker, J. M.,
W. D. Bowen,
R. R. Matsumoto,
B. De Costa,
and
K. C. Rice.
Sigma receptors: biology and function.
Pharmacol. Rev.
42:
355-402,
1990[Medline].