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Department of Physiology and Biophysics, Finch University of Health Sciences/ The Chicago Medical School, North Chicago, Illinois 60064
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The effect of metabotropic glutamate receptor (mGluR)
activation on vasopressin (VP) and oxytocin (OT) release was evaluated using explants of the hypothalamoneurohypophysial system.
(+/
)-1-Aminocyclopentane-trans-1,3-dicarboxylic acid
(t-ACPD), an agonist at groups I and II mGluRs, increased VP and OT
release in a concentration-dependent manner. A role for group I mGluRs
in VP and OT release was demonstrated by the ability of a group
I-specific mGluR antagonist, 1-aminoindan-1,5-idicarboxylic acid
(AIDA), to block the effect of t-ACPD and the ability of a group
I-specific agonist,
(R,S)-3,5-dihydroxyphenylglycine, to
significantly increase both VP (P = 0.0029) and OT
(P = 0.0032) release. However, AIDA did not alter VP or
OT release induced by a ramp increase in osmolality of the perifusion
medium. The role of group III mGluRs was examined using
L(+)-2-amino-4-phosphonobutyric acid (L-AP4), an agonist of these
receptors. L-AP4 did not change basal release of VP or OT and did not
prevent osmotically stimulated hormone release. Thus mGluR activation
stimulates VP and OT release, but it is not required for osmotic
stimulation of hormone release.
supraoptic nucleus; neurohypophysis; excitatory amino acids; osmotic stimulation
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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METABOTROPIC GLUTAMATE RECEPTORS (mGluRs) are classified into three groups based on sequence homology, pharmacology, and effectors. Group I includes mGluR1 and mGluR5 that are positively linked to phospholipase C (PLC), group II includes mGluR2 and mGluR3, and group III includes mGluR4,6,7,8. Both groups II and III are negatively linked to adenylate cyclase (for review, see Ref. 10). Electrophysiological, immunocytochemical, and in situ hybridization data support the presence and involvement of the mGluRs on both the presynaptic terminals in the supraoptic nucleus (SON) and the postsynaptic membranes of the magnocellular neurons of SON (5, 6, 11, 12, 22, 24). This strongly implicates a role of these receptors in VP and OT release, but the effect of mGluRs on release has yet to be examined directly.
The evidence for postsynaptic mGluRs on the SON neurons themselves
derives from whole cell patch-clamp and intracellular recording data
(11). Application of
trans-1-amino-1,3-cyclopentane dicarboxylic acid (t-ACPD), a
group I and II mGluR agonist, resulted in an inward current, a slow
depolarization, and a decrease in conductance in one-half of the
magnocellular neurons (11). A group I and II mGluR
antagonist,
(R,S)-
-methyl-4-carboxyphenylglycine, blocked these effects of t-ACPD. Both a specific group II-receptor agonist, 2S,1',2'S-2-carboxycyclopropylglycine, and a
group III agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), did
not alter these parameters (11). The group I mGluRs on SON
neurons mediate their effects by reducing the resting voltage-gated and
Ca2+-activated K+ currents (21).
The evidence points toward the presence of a group I mGluR on the
magnocellular neurons and supports the immunohistochemical evidence of
mGluR1b receptors in the SON (6).
Presynaptic effects of groups I and III mGluRs have been reported in the SON. The application of L-AP4, a group III-specific agonist, decreased the frequency of excitatory postsynaptic currents and inhibitory postsynaptic currents in the SON indicative of inhibition of both GABA and glutamate release from presynaptic terminals (11, 21). Similarly, t-ACPD and (R,S)-3,5-dihydroxyphenylglycine (DHPG), a group I mGluR-specific agonist, increased the frequency of both EPSCs and IPSCs in both vasopressin (VP) and oxytocin (OT) neurons. However, this effect was inhibited in the presence of tetrodotoxin (TTX), indicating a presynaptic location on the somas of local inhibitory, GABAergic, and excitatory glutamatergic neurons adjacent to the SON that innervate magnocellular neurons (1, 2, 11, 21). Thus neurons afferent to the SON neurons express multiple mGluRs that are differentially located. Specifically, mGluR group I receptors, possibly mGluR1, are on the somata and/or dendrites of local neurons that innervate the SON, and mGluR group III receptors, possibly mGluR7, are located on the terminals of these same neurons. Both of these receptors have been demonstrated to be present in the hypothalamus and are expressed in the SON (4-6).
In the current studies, various mGluR agonists and antagonists were evaluated for effects on VP and OT release from explants of the hypothalamoneurohypophysial system (HNS). The purpose was to extend the prior electrophysiological observations by examining the role of mGluRs in neuropeptide hormone release. The effects of t-ACPD (a group I and II mGluR agonist), DHPG (a specific group I agonist), and L-AP4 (an mGluR group III agonist) were evaluated. In addition, a selective group I antagonist, (R,S)-1-aminoindan-1,5-dicarboxylic acid/ UPF523 (AIDA), and L-AP4 were used to examine the possible involvement of mGluR groups I and III receptors in osmotic stimulation of VP and OT release.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Preparation and perifusion of HNS explants. HNS explants were obtained from decapitated male Sprague-Dawley rats (125-150 g). The explants included the OT and VP magnocellular neurons of the SON with their axonal projections extending through the median eminence and terminating in the neural lobe. The explants also included the organum vasculosum of the lamina terminalis (OVLT), the suprachiasmatic nucleus, and the arcuate nucleus. To prepare the explant, the brain was removed from the skull using a caudal approach to maintain the pituitary stalk intact. Under a dissecting microscope, the anterior pituitary was removed along with the dura mater and arachnoid layers. A block of tissue was removed by cutting rostral to the optic tracts, lateral to the median eminence, and caudal to the pituitary stalk. The explant is ~1- to 2-mm thick, and at the rostral end it is ~5-mm wide at its widest point.
HNS explants were perifused at 37°C with oxygenated culture medium. The explants were placed in closed chambers (0.5 ml) and perifused at a rate of 1.8-3.0 ml/h. The medium used was F12 nutrient mixture (GIBCO or Sigma). The medium was fortified with 20% fetal bovine serum, 1 mg/ml glucose, 50 U/ml penicillin, 50 µg/µl streptomycin, and 0.1 µM bacitracin. Bacitracin was used to prevent degradation of the OT and VP in the collected medium. Six explants were perifused simultaneously during each experiment. The medium from each chamber was collected at 5°C in a refrigerated fraction collector and stored at20°C until the OT or VP content was determined by radioimmunoassay. The explants were frozen in liquid nitrogen at the end of the experiment and stored at 80°C until extracted for RNA.
Experimental procedures. The explants were perifused for 4 h before application of any pharmacological agent or change in osmolality to allow the explant to equilibrate and to establish a basal rate of hormone release. Subsequent hormone release was normalized to the basal release of that explant at the end of the equilibration period and is expressed as a percentage of this basal value.
When explants were exposed to increased osmolality, the osmolality of the perifusate was increased over a 6-h period by 20-40 mosmol/kgH2O with a ramp increase in NaCl. NaCl was chosen as the osmotic agent because physiological changes in osmolality of the extracellular fluid primarily reflect changes in sodium. Although sodium may elicit specific responses, HNS explants have been shown to respond to increases in osmolality that are sodium independent (17). Therefore, the response to the ramp increase in NaCl cannot be considered as sodium specific, and thus it is referred to as an osmotic stimulus. Explants were exposed to the following mGluR agonists: t-ACPD (5-200 µM; Tocris), DHPG (50 µM; Tocris), and L-AP4 (50-300 µM; Tocris). AIDA, a group I mGluR antagonist (300 µM; Tocris), was also used. With the exception of DHPG, which is water soluble, stock solutions of these agents were prepared in 1 eq NaOH and then diluted into perifusion medium. A comparable amount of base was added to the medium for the control explants. This did not result in a noticeable change in pH (F12 medium contains phenol red as a pH indicator).Radioimmunoassay. VP and OT concentrations in the perifusate fractions were determined by radioimmunoassay as described previously (19). The antisera used were generated in conjunction with Arnel Products (Brooklyn, NY). The antibodies were used at final dilutions of 1:100,000-1:150,000. Duplicate 50- and 100-µl aliquots of each fraction were assayed. All samples from a given experiment were assayed at the same time. The minimum sensitivity was 1.0 pg/tube for VP and 0.5 pg/tube for OT.
RNA extraction and quantification. VP and OT mRNA content of the explants at the end of the perifusion period was determined by ribonuclease protection assay as described previously (20). A 32P-labeled full-length VP cRNA probe (680 bp) synthesized using the Promega Riboprotein System from the pGEM 4-AVP8C construct provided by T. G. Sherman, Georgetown University, was used in the assay. VP and OT mRNA could be assayed simultaneously, because the full-length VP mRNA probe includes the region of exon II that is homologous between VP and OT mRNA. This region codes a portion of neurophysin. Thus the protected fragments from VP and OT mRNA were different sizes (e.g., 680 vs. 200 bp, respectively) and could be separated on 1.3% agarose gel. Total extracted RNA from each explant was used in the hybridization.
VP and OT mRNA content was determined by counting the radioactivity in gel fragments containing the VP and OT mRNA bands. Standards of 0, 50, 100, 500, and 1,000 pg of sense VP mRNA generated from the cAVP-8C plasmid as well as RNA from a nonperifused explant and standard preparations of RNA from hydrated and dehydrated rats were included on each gel for comparison.Data analysis.
The results are expressed graphically as means of the percent of basal
release ± SE. Statistical significance was determined by two-way
ANOVA with repeated measures following log10 transformation of the data. When the ANOVA indicated statistical significance, individual mean comparisons were performed by simple effects or Newman-Keuls analysis to examine if the difference at specific time
points was significant. The level of significance was set at
P
0.05. On each figure, an arrow or a box indicates the
time when the HNS explants were exposed to each agent, F
values represent overall group differences, and symbols indicate the
probability that hormone release was different between groups at
individual time points.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Effect of t-ACPD on hormone release.
The role of groups I and II mGluRs in hormone release was evaluated by
perifusing explants with t-ACPD at various concentrations for 2 h
or longer. A concentration-dependent stimulation of both VP and OT
release was observed when the peak response to 5, 12.5, 25, or 100 µM
t-ACPD was evaluated (Fig. 1). Both VP
and OT releases were significantly increased compared with control
explants that received only perifusion medium.
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Effect of a group I mGluR antagonist, AIDA, on t-ACPD-induced
hormone release.
Due to the fact that t-ACPD is an agonist at both group I and group II
mGluRs, other agents were used to further elucidate the receptor type
responsible for the increase in hormone release. HNS explants were
exposed to t-ACPD for 4 h in the presence of the group I mGluR
antagonist AIDA. AIDA (300 µM) blocked the t-ACPD-induced (100 µM)
increase in both VP and OT release (Fig.
2, A and B). This
suggests that the effect of t-ACPD on VP and OT release is mediated
through activation of group I mGluRs.
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Effect of DHPG, a group I-specific mGluR agonist.
To further evaluate the role of group I mGluRs in VP and OT release, a
more specific agonist was applied to the HNS explants. Explants were
exposed to DHPG (50 µM), an agonist specific for group I mGluRs, for
4 h following the equilibration period. DHPG induced a significant
increase in both VP and OT release compared with the control groups
(Fig. 3, A and B).
This confirms that group I mGluRs increase VP and OT release, and it
suggests that this is the receptor type responsible for the effect of
t-ACPD.
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Effect of AIDA on osmotically stimulated hormone release.
To evaluate the role of the group I mGluRs in response to an osmotic
stimulus, HNS explants were exposed to a gradual increase in NaCl
concentration of 30 mosmol/kgH2O over a 6-h period in the
presence and absence of AIDA. AIDA was added immediately before initiating the ramp increase in osmolality. As shown in Fig.
4, A and B, the
increase in osmolality significantly stimulated VP and OT release. The
effect of the ramp increase in osmolality on VP and OT release was not
altered in the presence of AIDA (300 µM). Thus, unlike the ionotropic
GluRs (15, 19), group I mGluRs do not appear to be
essential for HNS explants to respond to an osmotic challenge. A subset
of explants evaluated for osmotic stimulation of hormone in the
presence and absence of AIDA (300 µM) was also evaluated for changes
in VP and OT mRNA content. AIDA did not significantly alter either VP
or OT mRNA (Fig. 5, A-C).
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Effect of group III mGluR agonist, L-AP4, on basal and osmotically stimulated hormone release. As described previously, the presynaptic location of the group III mGluRs provides the opportunity for these receptors to inhibit excitatory and inhibitory transmission to the VP and OT neurons. Because endogenous GABA release suppresses VP release from HNS explants (14), it was postulated that activation of group III mGluRs would inhibit GABA release resulting in an increase in VP release. To determine if group III mGluRs alter VP and OT release, L-AP4, a group III mGluR agonist, was applied sequentially at 50, 150, and 300 µM at 2-h intervals. There was no significant difference in VP or OT release compared with the control groups (data not shown).
Because glutamatergic afferents transmit information from the osmoreceptors to the VP and OT neurons in the SON, the presynaptic location of group III mGluRs also offers the potential for modulation of osmotic stimulation of hormone release. As in previous experiments, explants were exposed to a ramp increase in osmolality in the presence and absence of L-AP4 (300 µM). L-AP4 did not prevent VP and OT release in response to the osmotic stimulus (Fig. 6, A and B). Both VP and OT release significantly increased in explants exposed to an increase in osmolality in the presence of L-AP4 (300 µM) compared with the controls. Osmotically stimulated OT release was not significantly different in the presence and absence of L-AP4, but osmotically stimulated VP release was statistically slightly greater in the presence of L-AP4.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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These results demonstrate that the mGluRs are an important part of a complex system for activation of VP and OT release by excitatory amino acids. The release results are consistent with previous electrophysiological evidence for mGluR activation of the SON neurons as well as immunohistochemical evidence for receptor expression.
In the SON, t-ACPD has been shown to act postsynaptically both on magnocellular neurons and on afferent neurons that include both GABA and glutamate neurons. Application of 100 µM t-ACPD resulted in increased frequency of excitatory postsynaptic potentials (EPSPs) in 20% of cells recorded and of inhibitory postsynaptic potentials (IPSPs) in 50% of cells recorded. This effect could be blocked by TTX and mimicked by DHPG (50 µM) (12). In addition, t-ACPD also inhibited K+ conductance in SON neurons resulting in an inward current and slow depolarization (11). Similar effects have been seen in the hippocampus, dorsolateral septal nucleus, geniculate thalamus, nucleus of the solitary tract, cortex, and cerebellum where t-ACPD and DHPG can both induce slowly developing depolarization and an inward current associated with increases in cell firing (10). The overall effect of t-ACPD is an increase in excitability of the magnocellular neuron.
In the current studies, the observed increase in VP and OT release was probably due to the postsynaptic effects of t-ACPD and DHPG to depolarize magnocellular neurons. If the effect on local afferent neurons was dominant, the expectation would be to see an inhibition of release due to the larger number of presynaptic GABAergic terminals vs. glutamatergic in SON (8). This predominance of GABAergic innervation may be responsible for the greater percentage of IPSPs found electrophysiologically. Because the ACPD-induced depolarization of SON neurons is sufficient to elicit action potential firing, it would also be expected to result in an increase in hormone release as was observed in the current experiments. Other possible sites of action of t-ACPD and DHPG include the VP and OT nerve terminals in the posterior pituitary and glial cells in either the hypothalamus or pituitary. Although many agents modulate VP and OT release via direct actions on the nerve terminals in the posterior pituitary (for review, see Ref. 13), significant binding of H3-glutamate to mGluRs was not detected in the neural lobe (7). Thus this site is unlikely to account for the observed effects of t-ACPD via either actions on the terminals or on pituicytes. Expression of group I mGluRs has been reported on hippocampal astrocytes (18), and astrocytes are thought to play a dynamic role in regulating excitability of SON neurons. Therefore, glial involvement in the response to mGluR agonists is an intriguing possibility that could account for differences between electrophysiological and release responses such as the extended nature of the release induced by t-ACPD. However, further studies are required to substantiate the expression of mGluRs by SON astrocytes.
Another difference between electrophysiological and release results was the relative effectiveness of t-APCD and DHPG on VP compared with OT neurons. In the electrophysiological studies, a preferential effect on VP neurons compared with OT was reported: 80% of VP neurons responded to t-ACPD compared with 33% of identified OT neurons (11). In contrast, VP and OT release in response to either DHPG or t-ACPD was not substantially different.
The blockade of t-ACPD-induced VP and OT release by AIDA adds further support for the peptide release being mediated via activation of group I mGluRs, in particular mGluR1. Although AIDA does act preferentially at mGluR1, the concentration used in the current experiments (300 µM) is borderline for antagonist actions at mGluR5 as well (9). However, although mGluR5 expression has been reported in the hypothalamus (23), the strong expression of mGluR1b in the SON (6), the total blockade of t-ACPD-induced VP and OT release by AIDA, and the effect of DHPG support the conclusion that the t-ACPD effect is mediated via mGluR1. Although the possibility remains that a separate role for group II receptors might be demonstrated using a specific group II agonist, no effect of the specific group II agonist 2S,1',2'S-2 carboxycyclopropylglycine was observed electrophysiologically (11).
Recently, the specificity of some compounds considered to be specific agonists or antagonists for mGluRs has been questioned due to evidence that they alter responses of N-methyl-D-aspartate receptors (NMDA-Rs) (3). Specifically, activation of NMDA-Rs by high concentrations of some mGluR compounds probably reflected the presence of amino acid contaminants in the preparation (3). It is unlikely that such contamination accounts for the effects of the mGluR compounds reported in this study for the following reasons. Agonist effects of t-ACPD on NMDA-Rs were seen at 100 µM, but stimulation of VP and OT release was present at much lower concentrations of t-ACPD (5, 12.5, and 25 µM). For L-AP4, glycine contamination was thought to be responsible for NMDA-R agonist activity, but this was observed at a concentration of 1 mM, whereas the maximal amount used in the current experiments was 300 µM. DHPG caused a slight inhibition in NMDA-induced currents, but, in contrast, VP and OT release was increased, not decreased, by DHPG. As for AIDA, NMDA-induced currents were partially attenuated (~25%), but AIDA completely blocked t-ACPD-induced VP and OT release. Furthermore, AIDA did not alter osmotically stimulated VP and OT release, which is blocked by NMDA-R antagonists (19). Thus the possible actions of these compounds on NMDA-Rs do not appear to be a factor in interpreting their effects on hormone release.
As mentioned, osmotically stimulated VP and OT release was not prevented by blocking the postsynaptic group I mGluRs with AIDA or by blocking presynaptic group III mGluRs with L-AP4. Thus, despite the ability of group I mGluR agonists to induce VP and OT release, these receptors are not required for osmotic stimulation. Although it was originally hypothesized that group I mGluRs may enhance or extend the response initiated by ionotropic GluR (iGluR) or regulate gene expression, sustained increases in osmotically stimulated hormone release were evident in the presence of a concentration of AIDA able to block the effects of t-ACPD. Furthermore, the lack of a difference in mRNA content suggests that the osmotically induced increase in VP and OT mRNA was not compromised. Therefore, the data suggest that the ionotropic mechanisms are sufficient both for osmotically induced increases in hormone release and mRNA content.
Because glutamate mediates the osmotically induced increases in EPSPs that initiate action potentials in SON neurons and because there is evidence for the group III mGluRs, specifically mGluR7 expression, in the hypothalamus and SON (4), it was hypothesized that group III mGluRs might block osmotic stimulation of hormone release by preventing or attenuating glutamate release. However, this was not observed. Instead, there was a slight augmentation of basal and osmotically induced VP release by L-AP4. This could reflect inhibition of GABA release, because L-AP4 decreased the frequency of IPSPs in magnocellular neurons (12). However, this effect was small and was not evident in osmotically stimulated OT release or in basal release of either VP or OT. Thus these results indicate that the group III mGluRs do not play a major role in modulating either glutamate or GABA release from SON afferents in perifused HNS explants, and they do not interfere with osmotic stimulation of hormone release.
In conclusion, these results indicate a role for the mGluRs in VP and OT release with the postsynaptic activation of group I mGluRs in SON neurons being sufficient to elicit hormone release. Further evaluation of mGluR interactions with iGluRs is warranted to provide a better understanding of the specific role of these receptors in regulation of VP and OT hormone release.
Perspectives
VP and OT release from the neural lobe is regulated by a wide variety of neurotransmitters, neuropeptides, and hormones, as well as osmolality of the extracellular fluid. The role of the excitatory amino acid neurotransmitter glutamate in this complex is further complicated by its ability to interact with multiple receptors with both ionotropic and metabotropic signaling characteristics. The current study focused on the metabotropic class of these receptors and demonstrated stimulation of VP and OT release by a single group of mGluRs. It is significant that these receptors do not appear to participate in osmotic regulation of VP and OT release, because these responses are dependent on activation of ionotropic glutamate receptors. Also, other G protein-linked neuropeptide receptors have been shown to modulate osmotic stimulation of VP release (16). Thus the response is not mediated solely by ionotropic responses.| |
FOOTNOTES |
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Address for reprint requests and other correspondence: C. D. Sladek, Dept. of Physiology, Chicago Medical School, 3333 Green Bay Rd., North Chicago, IL 60064 (E-mail: sladekc{at}finchcms.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 24 October 2000; accepted in final form 12 April 2001.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Boudaba, C,
Schrader LA,
and
Tasker JG.
Physiological evidence for local excitatory synaptic circuits in the rat hypothalamus.
J Neurophysiol
77:
3396-3400,
1997
2.
Boudaba, C,
Szabo K,
and
Tasker JG.
Physiological mapping of local inhibitory inputs to the hypothalamic paraventricular nucleus.
J Neurosci
16:
7151-7160,
1996
3.
Contractor, A,
Gereau RW,
Green R,
and
Heinemann SF.
Direct effects of metabotropic glutamate receptor compounds on native and recombinant N-methyl-D-aspartate receptors.
Proc Natl Acad Sci USA
95:
8968-8974,
1998.
4.
Kinzie, JM,
Saugstad JA,
Westbrook GL,
and
Segerson TP.
Distribution of metabotropic glutamate receptor 7 messenger RNA in the developing and adult rat brain.
Neuroscience
69:
167-176,
1995[Web of Science][Medline].
5.
Kiss, J,
Gorc TJ,
Kuhn R,
Knopfel T,
Csaky A,
and
Halasz B.
Distribution of metabotropic glutamate receptor 1a in the rat hypothalamus: an immunocytochemical study using monoclonal and polyclonal antibody.
Acta Biol Hung
47:
221-237,
1996[Web of Science][Medline].
6.
Mateos, JM,
Azkue J,
Benitez R,
Sarria R,
Losada J,
Conquet F,
Ferraguti F,
Kuhn R,
Knopfel T,
and
Grandes P.
Immunocytochemical localization of the mGluR1b metabotropic glutamate receptor in the rat hypothalamus.
J Comp Neurol
390:
225-233,
1998[Web of Science][Medline].
7.
Meeker, RB,
Greenwood RS,
and
Hayward JN.
Glutamate receptors in the rat hypothalamus and pituitary.
Endocrinology
134:
621-629,
1994
8.
Meeker, RB,
Swanson DJ,
Greenwood RS,
and
Hayward JN.
Quantitative mapping of glutamate presynaptic terminals in the supraoptic nucleus and surrounding hypothalmus.
Brain Res
600:
112-122,
1993[Web of Science][Medline].
9.
Moroni, F,
Lombardi G,
Thomsen C,
Leonardi P,
Attucci S,
Peruginelli F,
Terregrossa SA,
Pellegrini-Giampietro DE,
Luneia R,
and
Pellicciari R.
Pharmacological characterization of 1-aminoindan-1,5-dicarboxylic acid, a potent mGluR1 antagonist.
J Pharmacol Exp Ther
281:
721-729,
1997
10.
Pin, JP,
and
Duvoisin R.
Review: neurotransmitter receptors. I. The metabotropic glutamate receptors: structure and functions.
Neuropharmacology
34:
1-26,
1995[Web of Science][Medline].
11.
Schrader, LA,
and
Tasker JG.
Modulation of multiple potassium currents by metabotropic glutamate receptors in neurons of the hypothalamic supraoptic nucleus.
J Neurophysiol
78:
3428-3437,
1997
12.
Schrader, LA,
and
Tasker JG.
Presynaptic modulation of metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons.
J Neurophysiol
77:
527-536,
1997
13.
Sladek, CD.
Antidiuretic hormone: synthesis and release.
In: Handbook of Physiology. The Endocrine System. Endocrine Regulation of Water and Electrolyte Balance. Bethesda, MD: Am Physiol Soc, 2000, sect. 7, vol. III, pt. 2, chapt. 12, p. 436-495.
14.
Sladek, CD,
and
Armstrong WE.
GABA antagonists stimulate vasopressin release from organ-cultured hypothalamo-neurohypophyseal explants.
Endocrinology
120:
1576-1580,
1987
15.
Sladek, CD,
Badre SE,
Morsette DJ,
and
Sidorowicz HE.
Role of non-NMDA receptors in osmotic and glutamate stimulation of vasopressin release: effect of rapid receptor desensitization.
J Neuroendocrinol
10:
897-903,
1998[Web of Science][Medline].
16.
Sladek, CD,
and
Joynt RJ.
Role of angiotensin in the osmotic control of vasopressin release by the organ-cultured rat hypothalamo-neurohypophyseal system.
Endocrinology
106:
173-178,
1980
17.
Sladek, CD,
and
Knigge KM.
Osmotic control of vasopressin release by organ cultured hypothalamo-neurohypophyseal explants from the rat.
Endocrinology
101:
1834-1838,
1977
18.
Steinhauser, C,
and
Gallo V.
News on glutamate receptors in glial cells.
Trends Neurosci
19:
339-345,
1996[Web of Science][Medline].
19.
Swenson, KL,
Badre SE,
Morsette DJ,
and
Sladek CD.
N-methyl-D-aspartic (NMDA) stimulation of vasopressin release: role in osmotic regulation and modulation by gonadal steroids.
J Neuroendocrinol
10:
679-685,
1998[Web of Science][Medline].
20.
Swenson, KL,
and
Sladek CD.
Gonadal steroid modulation of vasopressin secretion in response to osmotic stimulation.
Endocrinology
138:
2089-2097,
1997
21.
Tasker, JG,
Boudaba C,
and
Schrader LA.
Local glutamatergic and GABAergic synaptic circuits and metabotropic glutamate receptors in the hypothalamic paraventricular and supraoptic nuclei.
Adv Exp Med Biol
449:
117-121,
1998[Web of Science][Medline].
22.
Van den Pol, AN.
Metabotropic glutamate receptor mGluR1 distribution and ultrastructural localization in hypothalamus.
J Comp Neurol
349:
615-632,
1994[Web of Science][Medline].
23.
Van den Pol, AN,
Herman-Borgmeyer I,
Hofer M,
Ghosh P,
and
Heinemann S.
Ionotropic glutamate-receptor gene expression in hypothalamus: localization of AMPA, kainate, and NMDA receptor RNA with in situ hybridization.
J Comp Neurol
343:
428-444,
1994[Web of Science][Medline].
24.
Van den Pol, AN,
Kogelman L,
Ghosh P,
Liljelund P,
and
Blackstone C.
Developmental regulation of the hypothalamic metabotropic glutamate receptor mGluR1.
J Neurosci
14:
3816-3834,
1994[Abstract].
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  T. E. Lohmeier Neurohypophysial hormones Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R715 - R717. [Full Text] [PDF]
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H. M. Stauss Baroreceptor reflex function Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2002; 283(2): R284 - R286. [Full Text] [PDF]
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