Role Of Excitatory Amino Acids Research Articles

Socioeconomic Disadvantage, Chronic Stress, and Hippocampal Subfield Development in Children.

Recent findings indicate that hair cortisol concentrations significantly mediate associations between socioeconomic disadvantage and reduced hippocampal CA3 and dentate gyrus volumes in children. In this commentary, we discuss these results and highlight important future research directions, including focusing on hippocampal subfield structural development in relation to episodic memory and mental health; the mechanistic role of excitatory amino acids, such as glutamate; and how chronic stress and cognitive stimulation may make unique proximal contributions to socioeconomic differences in hippocampal subfield volume. Building on the findings in these ways will contribute to advances in strategies aimed at reducing socioeconomic disparities in academic achievement and mental health.

5-HT1A Receptor Agonist Promotes Retinal Ganglion Cell Function by Inhibiting OFF-Type Presynaptic Glutamatergic Activity in a Chronic Glaucoma Model.

Serotonin receptors are potential neuroprotective agents in degenerative diseases of the central nervous system. The protective effects of serotonin receptor (5-HT1A) agonists on the survival and function of retinal ganglion cells (RGCs) by regulating the release of the presynaptic neurotransmitter γ-aminobutyric acid (GABA) were confirmed in our previous study of a chronic glaucoma rat model. However, the roles of excitatory amino acids and their interactions with the 5-HT1A receptor in glaucoma remain unknown. Here, we found that ocular hypertension increased glutamine synthetase (GS) and excitatory amino acid transporter 2 (EAAT2) expression in rat retinas. In addition, the high expression of GS and EAAT2 induced by glaucoma was downregulated by the 5-HT1A receptor agonist 8-OH-DPAT and the 5-HT1A receptor antagonist WAY-100635, respectively. Patch-clamp techniques were used to record glutamate receptor-mediated spontaneous and miniature glutamatergic excitatory post-synaptic currents (sEPSCs and mEPSCs) as well as L-glutamate-induced current in OFF-type and ON-type RGCs in rat retinal slices. Although there were no significant differences in the frequency and amplitude of sEPSC and mEPSC release between normal and glaucoma OFF- and ON-type RGCs, exogenous 8-OH-DPAT administration specifically reduced the frequency, but not the amplitude, of sEPSC and mEPSC release in glaucoma OFF-type rather than ON-type RGCs; these effects were completely blocked by WAY-100635. In summary, 8-OH-DPAT decreases and increases GS and EAAT2 expression of glaucomatous retina, respectively, while decreasing sEPSC and mEPSC frequency. In contrast, WAY-100635 increases and decreases GS and EAAT2 expression of glaucomatous retina, respectively, while increasing sEPSC and mEPSC frequency. The reduction of glutamatergic presynaptic transmission by 8-OH-DPAT deactivates RGCs at the neural network level and reduces the excitotoxic damage in the pathological process of chronic glaucoma.

Regulation of Excitatory Amino Acid Transmission in the Retina: Studies on Neuroprotection.

Excitotoxicity occurs in neurons due to the accumulation of excitatory amino acids such as glutamate in the synaptic and extrasynaptic locations. In the retina, excessive glutamate concentrations trigger a neurotoxic cascade involving several mechanisms, including the elevation of intracellular calcium (Ca2+) and the activation of α-amino-3-hydroxy 5-methyl-4-iso-xazole-propionic acid/kainate (AMPA/KA) and N-methyl-d-aspartate (NMDA) receptors leading to retinal degeneration. Both ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs) are present in the mammalian retina. Indeed, due to the abundant expression of GluRs, the mammalian retina is highly susceptible to excitotoxic neurodegeneration. Excitotoxicity has been postulated to present a common downstream mechanism for several stimuli, including hypoglycemia, hypoxia, ischemia, and chronic neurodegenerative diseases. Experimental approaches to the study of neuroprotection in the retina have utilized insults that trigger hypoxia, hypoglycemia, or excitotoxicity. Using these experimental approaches, the neuroprotective potential of GluR agents, including the NMDA receptor modulators (MK801, ifenprodil, memantine); AMPA/KA receptor antagonist (CNQX); Group II and III mGluR agonists (LY354740, quisqualate); and Ca2+-channel blockers (diltiazem, lomerizine, verapamil, ω-conotoxin), and others (pituitary adenylate cyclase activating polypeptide, neuropeptide Y, acetylcholine receptor agonists) have been elucidated. In addition to corroborating the exocytotic role of excitatory amino acids in retinal degeneration, these studies affirm that multiple mechanism/s contribute to the prevention of damage caused by excitotoxicity in the retina. Therefore, it is feasible that several pathways are involved in protecting the retina from toxic insults in ocular neurodegenerative conditions such as glaucoma and retinal ischemia. Furthermore, these experimental models are viable tools for evaluating therapeutic candidates in ocular neuropathies.

N-Methyl-d-aspartate Receptor Mechanosensitivity Is Governed by C Terminus of NR2B Subunit

N-methyl-D-aspartate receptors (NMDARs), critical mediators of both physiologic and pathologic neurological signaling, have previously been shown to be sensitive to mechanical stretch through the loss of its native Mg(2+) block. However, the regulation of this mechanosensitivity has yet to be further explored. Furthermore, as it has become apparent that NMDAR-mediated signaling is dependent on specific NMDAR subtypes, as governed by the identity of the NR2 subunit, a crucial unanswered question is the role of subunit composition in observed NMDAR mechanosensitivity. Here, we used a recombinant system to assess the mechanosensitivity of specific subtypes and demonstrate that the mechanosensitive property is uniquely governed by the NR2B subunit. NR1/NR2B NMDARs displayed significant stretch sensitivity, whereas NR1/NR2A NMDARs did not respond to stretch. Furthermore, NR2B mechanosensitivity was regulated by PKC activity, because PKC inhibition reduced stretch responses in transfected HEK 293 cells and primary cortical neurons. Finally, using NR2B point mutations, we identified a PKC phosphorylation site, Ser-1323 on NR2B, as a unique critical regulator of stretch sensitivity. These data suggest that the selective mechanosensitivity of NR2B can significantly impact neuronal response to traumatic brain injury and illustrate that the mechanical tone of the neuron can be dynamically regulated by PKC activity.

Role of Excitatory Amino Acid Transporter‐2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics

Glutamate is an essential excitatory neurotransmitter regulating brain functions. Excitatory amino acid transporter (EAAT)-2 is one of the major glutamate transporters expressed predominantly in astroglial cells and is responsible for 90% of total glutamate uptake. Glutamate transporters tightly regulate glutamate concentration in the synaptic cleft. Dysfunction of EAAT2 and accumulation of excessive extracellular glutamate has been implicated in the development of several neurodegenerative diseases including Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Analysis of the 2.5 kb human EAAT2 promoter showed that NF-κB is an important regulator of EAAT2 expression in astrocytes. Screening of approximately 1,040 FDA-approved compounds and nutritionals led to the discovery that many β-lactam antibiotics are transcriptional activators of EAAT2 resulting in increased EAAT2 protein levels. Treatment of animals with ceftriaxone (CEF), a β-lactam antibiotic, led to an increase of EAAT2 expression and glutamate transport activity in the brain. CEF has neuroprotective effects in both in vitro and in vivo models based on its ability to inhibit neuronal cell death by preventing glutamate excitotoxicity. CEF increases EAAT2 transcription in primary human fetal astrocytes through the NF-κB signaling pathway. The NF-κB binding site at -272 position was critical in CEF-mediated EAAT2 protein induction. These studies emphasize the importance of transcriptional regulation in controlling glutamate levels in the brain. They also emphasize the potential utility of the EAAT2 promoter for developing both low and high throughput screening assays to identify novel small molecule regulators of glutamate transport with potential to ameliorate pathological changes occurring during and causing neurodegeneration.

Kynurenic acid blocks chemogenic nociception

Previous studies have suggested a role of excitatory amino acids (EAA) in nociception. In the present study the effects of two antagonists of EAA-receptors on capsaicin-induced eye wipings were investigated. Intracisternally administered kynurenic acid, in contrast to intravenously administered MK-801, was found to effectively block the induced eye wipings. It is proposed that EAA, by activating non-NMDA receptors, are involved in the transmission of chemogenic nociception.

Math1 Is Essential for the Development of Hindbrain Neurons Critical for Perinatal Breathing

Mice lacking the proneural transcription factor Math1 (Atoh1) lack multiple neurons of the proprioceptive and arousal systems and die shortly after birth from an apparent inability to initiate respiration. We sought to determine whether Math1 was necessary for the development of hindbrain nuclei involved in respiratory rhythm generation, such as the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN), defects in which are associated with congenital central hypoventilation syndrome (CCHS). We generated a Math1-GFP fusion allele to trace the development of Math1-expressing pFRG/RTN and paratrigeminal neurons and found that loss of Math1 did indeed disrupt their migration and differentiation. We also identified Math1-dependent neurons and their projections near the pre-Bötzinger complex, a structure critical for respiratory rhythmogenesis, and found that glutamatergic modulation reestablished a rhythm in the absence of Math1. This study identifies Math1-dependent neurons that are critical for perinatal breathing that may link proprioception and arousal with respiration.

The Roles of Excitatory Amino Acids and Cytokines in Morphine Tolerance: Effect of Tricyclic Antidepressant Amitriptyline

Morphine is an effective analgesic in clinical practice; however, its long-term administration causes tolerance, thereby limiting its use. The development of opioid tolerance and its associated hyperalgesia has been associated with interactions between opioid receptors and excitatory amino acids or cytokines. Targeted inhibition of excitatory amino acid- and cytokine-mediated signaling pathways may allow development of novel therapeutic strategies for treating opioid tolerance. Recent studies showed that administration of amitriptyline (a tricyclic antidepressant widely used in the treatment of neuropathic pain) attenuated morphine tolerance and preserved the antinociceptive effect of morphine. This ability might be related to the effects of tricyclic antidepressants on pro-inflammatory cytokine release and glutamate transporter expression in dorsal horn during morphine tolerance. Here, we will review evidence for the role of excitatory amino acids and cytokines in the development of morphine tolerance and discuss potential mechanisms by which tricyclic antidepressants attenuate morphine tolerance.

Role of excitatory amino acids in the mediation of tracheobronchial cough induced by citric acid inhalation in the rabbit

We investigated the role of ionotropic glutamate receptors located within the caudal portions of the nucleus tractus solitarii (cNTS) and the caudal ventral respiratory group (cVRG) in the mediation of coughing evoked by citric acid inhalation in spontaneously breathing rabbits under pentobarbitone anaesthesia. Bilateral microinjections (30–50 nl) of 10 mM CNQX and 10 mM D-AP5 were performed to block non-NMDA and NMDA receptors, respectively. An attempt was also made to investigate the effects of ionotropic glutamate receptor blockade within the cVRG on sneezing induced by mechanical stimulation of the nasal mucosa. Blockade of non-NMDA receptors within the cNTS abolished coughing and associated tachypneic responses, while blockade of NMDA receptors only reduced cough responses. Blockade of non-NMDA receptors within the cVRG always abolished spontaneous rhythmic abdominal activity as well as coughing and associated tachypneic responses; blockade of NMDA receptors only reduced spontaneous rhythmic abdominal activity and coughing. As to sneezing, blockade of non-NMDA receptors within the cVRG suppressed the expiratory thrusts without affecting the inspiratory preparatory bursts, while blockade of NMDA receptors only strongly attenuated the expiratory thrusts. This study is the first to provide evidence that ionotropic glutamate receptors, and especially non-NMDA receptors, are involved in the mediation of coughing induced by citric acid inhalation and to suggest that citric acid-activated cough-related afferents terminate within the cNTS. Present data also corroborate the notion that the cVRG is involved in the generation of the whole cough motor pattern, but seems to represent merely an expiratory output system for sneezing.

Joint pain

Both inflammatory and degenerative diseases of joints are major causes of chronic pain. This overview addresses the clinical problem of joint pain, the nociceptive system of the joint, the mechanisms of peripheral and central sensitization during joint inflammation and long term changes during chronic joint inflammation. While the nature of inflammatory pain is obvious the nature and site of origin of osteoarthritic pain is less clear. However, in both pathological conditions mechanical hyperalgesia is the major pain problem, and indeed, both joint nociceptors and spinal nociceptive neurons with joint input show pronounced sensitization for mechanical stimulation. Molecular mechanisms of mechanical sensitization of joint nociceptors are addressed with an emphasis on cytokines, and molecular mechanisms of central sensitization include data on the role of excitatory amino acids, neuropeptides and spinal prostaglandins. The overview will also address long-term changes of pain-related behavior, response properties of neurons and receptor expression in chronic animal models of arthritis.

On the Horizon From the ORS

On the Horizon From the ORS

Increase in excitatory amino acid concentration and transporters expression in osteoarthritic knees of anterior cruciate ligament transected rabbits

The present study aimed to determine the role of excitatory amino acids (EAAs) and EAA transporters (EAATs) in an osteoarthritis (OA) model of rabbit knees. OA was induced in New Zealand white male rabbits by anterior cruciate ligament transection (ACLT) in one knee of one hind limb; the other knee left unoperated. Rabbits that received ACLT of knee were assigned to the ACLT group (n=6), while a sham-operated group (n=6) underwent arthrotomy with no ACLT. Six naïve rabbits that received no surgery were used as normal control. The width of the knee joint was measured to determine the severity of joint inflammation. Before operation and at 10, 20, and 30 weeks after operation, knee joint dialysates were collected by microdialysis and assayed for EAAs by high-performance liquid chromatography. Gross morphology and histopathology and EAATs glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) expression in the articular cartilage of the knees were evaluated by immunohistochemistry and western blot analysis. In the ACLT knees, a significant increase in the joint width was observed (5.3+/-0.9 mm, P<0.05) at 30 weeks after operation, while the sham-operated and naïve knees showed no difference as compared with the basal values. The concentrations (microM) of aspartate and glutamate in knee dialysates at 30 weeks after ACLT in naïve, sham, and ACLT were 0.36+/-0.07 and 4.5+/-1.10; 0.38+/-0.09 and 4.61+/-1.11; 0.67+/-0.18 and 9.71+/-2.89, respectively. Levels of glutamate and aspartate in the dialysates obtained from the ACLT knees increased by 213.3+/-29.6% and 187.5+/-33.8% (P<0.05) when compared to those in the sham-operated knees. Both naïve and ACLT chondrocytes were positively stained by antibodies against GLAST and GLT-1. GLAST and GLT-1 protein expressions were significantly increased in the ACLT knees (P<0.05). Our findings indicate an involvement of EAAs and EAATs in the pathogenesis of OA in ACLT rabbits.

The role of excitatory amino acids and substance P in the mediation of the cough reflex within the nucleus tractus solitarii of the rabbit

We hypothesized that cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit is primarily mediated by glutamatergic neurotransmission at the level of the caudal portions of the medial subnucleus of the nucleus tractus solitarii (NTS) and the lateral commissural NTS where cough-related afferents terminate, and that this reflex is potentiated by local release of substance P. To test our hypothesis, we performed bilateral microinjections (30–50 nl) of ionotropic glutamate receptor antagonists or substance P into these locations in pentobarbitone anaesthetized, spontaneously breathing rabbits. Blockade of NMDA and non-NMDA receptors by 50 mM kynurenic acid abolished the cough reflex without affecting the Breuer–Hering inflation reflex or the pulmonary chemoreflex. Blockade of non-NMDA receptors using 10 mM CNQX or 5 mM NBQX caused identical effects. Blockade of NMDA receptors by 10 mM D-AP5 strongly reduced, but did not abolish cough responses. Microinjections of 1 mM substance P increased peak and rate of rise of abdominal muscle activity as well as cough number. These results are the first to provide evidence that ionotropic glutamate receptors, especially non-NMDA receptors, located within specific regions of NTS are primarily involved in the mediation of cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit. Present findings on substance P cough-enhancing effects extend previous observations and are relevant to the tachykinin-mediated central sensitization of the cough reflex. They also may provide hints for further studies on centrally acting antitussive drugs.

Preventive effects of intrathecal methylprednisolone administration on spinal cord ischemia in rats: The role of excitatory amino acid metabolizing systems

Spinal cord ischemic injury usually results in paraplegia, which is a major cause of morbidity after thoracic aorta operations. Ample evidence indicates that massive release of excitatory amino acids (EAAs; glutamate) plays an important role in the development of neuronal ischemic injuries. However, there is a lack of direct evidence to indicate the involvement of EAAs in the glutamate metabolizing system (including the glutamate transporter isoforms, i.e. the Glu-Asp transporter (GLAST), Glu transporter-1 (GLT-1), and excitatory amino acid carrier one (EAAC1); glutamine synthetase (GS); and glutamate dehydrogenase (GDH)) in spinal cord ischemia. In the present results, we found that methylprednisolone (MP; intrathecal (i.t.) injection, 200 μg twice daily administered for 3 days before ischemia), a synthetic glucocorticoid, is the therapeutic agent for the treatment of spinal injuries in humans, can significantly reduce the ischemia-induced motor function defect and down-regulate the glutamate metabolizing system (including GLAST, GLT-1, GS, and GDH) in male Wistar rats. The spinal cord ischemia-induced down-regulation of EAAC1 protein expression in the ventral portion of the lumbar spinal cord was partly inhibited by pretreatment with i.t. MP. However, MP did not affect the down-regulation of EAAC1 in the dorsal portion of the lumbar spinal cord after spinal cord ischemia. The i.t. injection of MP alone did not change the neurological functions and the expression of proteins of the glutamate metabolizing system in the spinal cord. Our results indicate that spinal cord ischemia-induced neurological deficits accompany the decrease in the expression of proteins of the glutamate metabolizing system in the lumbar portion of the spinal cord. The i.t. MP pretreatment significantly prevented these symptoms. These results support the observation that MP delivery through an i.t. injection, is beneficial for the treatment of spinal cord ischemic injuries.

A Role for Excitatory Amino Acids in Diabetic Eye Disease

Diabetic retinopathy is a leading cause of vision loss. The primary clinical hallmarks are vascular changes that appear to contribute to the loss of sight. In a number of neurodegenerative disorders there is an appreciation that increased levels of excitatory amino acids are excitotoxic. The primary amino acid responsible appears to be the neurotransmitter glutamate. This review examines the nature of glutamatergic signaling at the retina and the growing evidence from clinical and animal model studies that glutamate may be playing similar excitotoxic roles at the diabetic retina.

Hyperthermia influences excitatory and inhibitory amino acid neurotransmitters in the central nervous system. An experimental study in the rat using behavioural, biochemical, pharmacological, and morphological approaches

Role of excitatory amino acids, glutamate, aspartate, and inhibitory amino acids, gamma aminobutyric acid (GABA) and glycine in brain damage caused by heat stress was examined in a rat model. Subjection of rats to 4 h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator resulted in a marked increase in glutamate and aspartate in some brain regions, whereas a significant decline in GABA and glycine was observed in several brain areas. Profound behavioural alterations and impairment of motor and cognitive functions were seen at this time. Breakdown of the blood-brain barrier (BBB), reduction in regional cerebral blood flow (CBF), edema formation and cell injuries are prominent in several parts of the brain. Pretreatment with multiple opioid receptor antagonist, naloxone (10 mg/kg, i.p.) significantly restored the heat stress induced decline in GABA and glycine and thwarted the elevation of glutamate and aspartate in various brain areas. The motor or cognitive deficits were also attenuated. A significant reduction in BBB permeability, cerebral blood flow abnormalities, edema formation and cell injuries was evident. These novel observations suggest that (i) glutamate, aspartate, GABA and glycine are involved in the pathophysiology of heat stress, and (ii) a balance between excitatory and inhibitory amino acids in brain is crucial in hyperthermia induced brain injuries or repair.

Respiratory responses evoked by blockades of ionotropic glutamate receptors within the Bötzinger complex and the pre‐Bötzinger complex of the rabbit

The respiratory role of excitatory amino acid (EAA) receptors within the Bötzinger complex (BötC) and the pre-Bötzinger complex (pre-BötC) was investigated in alpha-chloralose-urethane anaesthetized, vagotomized, paralysed and artificially ventilated rabbits by using bilateral microinjections (30-50 nL) of EAA receptor antagonists. Blockade of both N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors by 50 mM kynurenic acid (KYN) within the BötC induced a pattern of breathing characterized by low-amplitude, high-frequency irregular oscillations superimposed on tonic phrenic activity and successively the disappearance of respiratory rhythmicity in the presence of intense tonic inspiratory discharges (tonic apnea). KYN microinjections into the pre-BötC caused similar respiratory responses that, however, never led to tonic apnea. Blockade of NMDA receptors by D(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 1, 10 and 20 mM) within the BötC induced increases in respiratory frequency and decreases in peak phrenic amplitude; the highest concentrations caused tonic apnea insensitive to chemical stimuli. Blockade of non-NMDA receptors by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1, 10 and 20 mM) within the BötC produced only less pronounced increases in respiratory frequency. Responses to D-AP5 in the pre-BötC were similar, although less pronounced than those elicited in the BötC and never characterized by tonic apnea. In the same region, CNQX provoked increases in respiratory frequency similar to those elicited in the BötC, associated with slight reductions in peak phrenic activity. The results show that EAA receptors within the investigated medullary subregions mediate a potent control on both the intensity and frequency of inspiratory activity, with a major role played by NMDA receptors.

Regulatory Role of Excitatory Amino Acids in Reproduction

Glutamate, the major excitatory amino acid (EAA) transmitter in the central nervous system, has been implicated as a critical mediator in brain function. Glutamate and its receptors are found in all key hypothalamic areas critically involved in reproduction. Administration of glutamate and its agonists can bring about LH release in animals with a steroid background. Antagonists of the ionotropic glutamate receptors inhibited LH release and abolished the steroid-induced and the preovulatory LH surge. Both NMDA and non-NMDA receptor antagonists can also inhibit pulsatile LH release in castrated animals. The preoptic area has been implicated as a primary site of action of NMDA, while non-NMDA agonists have been suggested to act primarily at the arcuate/median eminence level. While EAAs may act directly on GnRH neurons to enhance GnRH release, the majority of evidence suggests that an indirect mechanism, involving EAA activation of nitric oxide and/or catecholamines, plays a major role in the GnRH-releasing effects of EAAs. Furthermore, there is also some evidence that the tonic inhibitory effect of opioids on GnRH may also involve, at least in part, a suppression of glutamate. Finally, EAA stimulation of GnRH/LH release is markedly attenuated in middle-aged rats, suggesting that a defect in glutamate neurotransmission may underlie the attenuated LH surge observed in aging.

Role of Excitatory Amino Acids in the Control of Growth Hormone Secretion

Excitatory amino acids (EEAs), such as glutamate, are pivotal elements in the hypothalamic circuitry involved in the control of pituitary function. The actions of EEAs are mediated by different postsynaptic receptor subtypes, which include the ionotropic receptors N-methyl-D-aspartate (NMDA), kainate (KA), 2-amino-3-hydroxy- 5 methyl-4-isoxazol propionic acid (AMPA), as well as metabotropic receptors. In this review, we summarize the experimental work on the role of EAA neurotransmission in the control of GH secretion in the rat. Detailed characterization of the effects of agonists and antagonists of glutamate receptors on GH release revealed that activation of NMDA, KA, and AMPA receptors at different age-points resulted in clear-cut stimulation of GH secretion, although age- and sex-dependent differences were detected in the pattern of response to the different agonists. This stimulatory action was proven nitric oxide (NO)-dependent and not exerted at the pituitary level. Moreover, the effects of NMDA on GH release likely involve additional mediators other than hypothalamic GH-releasing hormone (GHRH). In contrast, the role of metabotropic receptors seems to be marginal, and only inhibitory actions were observed after activation of different receptor subtypes. Furthermore, evidence was obtained on the modulation of the EEA system by gonadal factors in the control of GH secretion, and on the physiological relevance of EEA pathways in the regulation of pulsatile GH release. The analysis of interactions between EAA receptors and other neuronal pathways evidenced the close interactions between different systems involved in the control of GH secretion. Blockade of glutamate receptors abolished the stimulatory effect of GABA and ghrelin on GH secretion and, inversely, blockade of ghrelin or GABA receptors abolished the stimulatory effect of EAAs. In conclusion, our data using the rat as animal model provide evidence for a pivotal role of glutamate pathways in the regulation of GH secretion throughout the life-span.

Tonic glutamatergic drive of RVLM vasomotor neurons?

the rostral ventrolateral medulla (RVLM) plays a critical role in the maintenance of baseline arterial pressure (AP) in all species in which it has been examined, and it appears to be the primary site responsible for the tonic supraspinal drive of sympathetic vasomotor outflow and AP, at least in