Tryptophan Metabolites in Irritable Bowel Syndrome: An Overnight Time-course Study

BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) often report poor sleep quality. Whether poor sleep is associated with tryptophan (Trp) metabolites is unknown. We compared serum Trp metabolites in women with IBS and healthy controls (HCs) using targeted liquid chromatography mass spectrometry (LC-MS)-based profiling. In IBS only, we explored whether Trp metabolites are associated with IBS symptoms and subjective and objective sleep indices, serum cortisol, plasma adrenocorticotropic hormone (ACTH), and cortisol/ACTH levels. METHODS: Blood samples were obtained every 80 minutes in 21 HCs and 38 IBS subjects following an anticipation-of-public-speaking stressor during a sleep laboratory protocol. Subjects completed symptom diaries for 28 days. Adjacent values of metabolites were averaged to represent 4 time-periods: awake, early sleep, mid-sleep, and mid-to-late sleep. Thirteen of 20 targeted Trp metabolites were identified. RESULTS: Ten of 13 Trp metabolites decreased across the night, while nicotinamide increased in both groups. A MANOVA omnibus test performed after principal component analysis showed a significant difference in these 13 principal component (P = 0.014) between groups. Compared to HCs, nicotinamide levels were higher and indole-3-lactic acid levels lower in the IBS group. Melatonin and indole-3-acetic acid levels were associated with several subjective/objective sleep measures; decreased stool consistency/frequency and abdominal pain were positively associated with melatonin and serotonin in the IBS group. The kynurenine and kynurenic acid were associated with ACTH (positively) and cortisol/ACTH (negatively). CONCLUSIONS: Nighttime Trp metabolites may provide clues to poor sleep and stress with IBS. Further study of the mechanism of metabolite action is warranted.

Correlation between kynurenine metabolites and postpartum depression / 中南大学学报(医学版)

To explore the correlation between kynurenine (KYN) metabolites and postpartum depression (PPD), and to provide new possible explanation for the pathogenesis of postpartum depression (PPD).
 Methods: A total of 726 Chinese women, who received cesarean section, were enrolled in this study. PPD was diagnosed with an Edinburgh Postnatal Depression Scale (EPDS) score ≥13. Twenty-four women with PPD and 48 matched women without PPD were randomly selected. The perinatal serum concentrations of KYN, quinolinic acid (QUIN) and kynurenic acid (KYNA) were measured. Subsequently, the puerperants were compared for the differences in the serum concentrations of KYN, QUIN and KYNA at the end of term, day 1 and day 3 after cesarean section, respectively.
 Results: The incidence of PPD was 7.99%. Of clinical characteristics, pressure during pregnancy was significantly different between subjects with or without PPD (P<0.01). Patients with PPD showed significantly increased serum KYN concentration (P<0.05) at the end of term, increased serum QUIN concentration (P<0.05) and decreased KYNA concentration (P<0.05) on the third day after cesarean section as compared with the control women. Furthermore, the KYNA/QUIN ratio was significantly higher in patients with PPD as compared to the control women on the third day after cesarean section (P<0.01).
 Conclusion: The contribution of alterations in plasma levels of KYN, QUIN and KYNA is closely related with the incidence of PPD, and correction of KYNA/QUIN ratio could be a new strategy for the prevention and treatment of postpartum depressive symptoms.

High-Fat Diet and Voluntary Chronic Aerobic Exercise Recover Altered Levels of Aging-Related Tryptophan Metabolites along the Kynurenine Pathway

Tryptophan metabolites regulate a variety of physiological processes, and their downstream metabolites enter the kynurenine pathway. Age-related changes of metabolites and activities of associated enzymes in this pathway are suggestable and would be potential intervention targets. Blood levels of serum tryptophan metabolites in C57BL/6 mice of different ages, ranging from 6 weeks to 10 months, were assessed using high-performance liquid chromatography, and the enzyme activities for each metabolic step were estimated using the ratio of appropriate metabolite levels. Mice were subjected to voluntary chronic aerobic exercise or high-fat diet to assess their ability to rescue age-related alterations in the kynurenine pathway. The ratio of serum kynurenic acid (KYNA) to 3-hydroxylkynurenine (3-HK) decreased with advancing age. Voluntary chronic aerobic exercise and high-fat diet rescued the decreased KYNA/3-HK ratio in the 6-month-old and 8-month-old mice groups. Tryptophan metabolites and their associated enzyme activities were significantly altered during aging, and the KYNA/3-HK ratio was a meaningful indicator of aging. Exercise and high-fat diet could potentially recover the reduction of the KYNA/3-HK ratio in the elderly.

The tryptophan utilization concept in pregnancy

The decrease in maternal plasma total (free + albumin-bound) tryptophan (Trp) during the third pregnancy trimester is attributed to induction of indoleamine 2,3-dioxygenase (IDO). When measured, free [Trp] is increased because of albumin depletion and non-esterified fatty acid elevation. The Trp depletion concept in pregnancy is therefore not supported because of incorrect interpretation of changes in Trp disposition and also for not addressing mouse strain differences in Trp-related responses and potential inhibition of Trp transport by the IDO inhibitor 1-methyl tryptophan. Application of the Trp utilization concept in pregnancy offers several physiological advantages favoring fetal development and successful outcome, namely provision of Trp for fetal protein synthesis and growth, serotonin for signaling pathways, kynurenic acid for neuroprotection, quinolinic acid for NAD+ synthesis, and other kynurenines for suppression of T cell responses. An excessive increase in Trp availability could compromise pregnancy by undermining T cell suppression, e.g., in pre-eclampsia.

Chemical constituents contained in seeds of Notopterygium franchetii / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents from the seeds of Notopterygium franchetii.</p><p><b>METHOD</b>Ethanol extracts of seeds N. franchetii were separated and purified by such methods as normal and reversed phase column chromatographies and thin-layer chromatography and structurally elucidated by MS and NMR evidences.</p><p><b>RESULT</b>Twenty nine compounds were separated, they were isoimperatorin (1), [3-sitosterol (2), phellopterin (3), bergapten (4), N-tetra, hexa, octacosanoylanthranilic acid (5-7), daucosterol (8), oxypeucedanin hydrate (9), umbelliferone (10), demethylfuropinnarin (11), (2S, 3S, 4R, 8E)-2-[(2'R)- 2'-hydroxydoco, trico, tetraco, entaco, hexaco sanosylamino] -octadecene-1, 3, 4-triol (12-16), (-)-oxypeucedanin (17), diosmetin (18), bergaptol-O-beta-D-glucopyranoside (19), nodakenin (20), 1'-O-beta-D-glucopyranosyl-(2R, 3S)-3-hydroxynodakenetin (21), uracil (22), decuroside V (23), 8-O-beta-D-glucopyranosyl-5-hydroxypsoralen (24), 8-O-beta-D-glucopyranosyl-5-methoxylpsoralen (25), diosmin (26), alaschanioside C (27), kynurenic acid (28) and mannitol (29).</p><p><b>CONCLUSION</b>All of these compounds were separated from the seeds of N. franchetii for the first time. Of them, 18, 22, 26 and 29 were firstly obtained from genus Notopterygium.</p>

Cytokines and Depression

Accumulating evidence has suggested the existence of reciprocal communication between immune, endocrine, and neurotransmitter system. Cytokine hypothesis of depression implies that increased pro-inflammatory cytokine such as -1, IL-6, IL-12, TNF-alpha, and IFN-gamma in major depression, acting neuromodulators, play a key role in the mediation of behavioral, neuroendocrine, and neurochemical disturbances in depression. Concerning the relation between cytokines and serotonin metabolism, pro-inflammatory cytokines have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase(IDO) that metabolizes tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The neurodegeneration process is reinforced by the neurotoxic effect of the hypercortisolemia during depression. From this perspective, it is possible that efficacy of antidepressants in the treatment of depression may, at least in part, rely on downregulation of pro-inflammatory cytokine synthesis. So, the use of cytokine synthesis inhibitors or cytokine antagonists may be a new treatment approach in depression. However, at present the question whether cytokines play a causal role in the onset of depression or are mere epiphenomena sustaining depressive symptoms remains to be elucidated. Nevertheless, cytokine hypothesis has created new perspectives in the study of psychological and pathophysiological mechanism that are associated with major depression, as well as the prospect for developing a new generation antidepressants.

Functional Connectivity Map of Retinal Ganglion Cells for Retinal Prosthesis

Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Among the many issues for prosthesis development, stimulation encoding strategy is one of the most essential electrophysiological issues. The more we understand the retinal circuitry how it encodes and processes visual information, the greater it could help decide stimulation encoding strategy for retinal prosthesis. Therefore, we examined how retinal ganglion cells (RGCs) in in-vitro retinal preparation act together to encode a visual scene with multielectrode array (MEA). Simultaneous recording of many RGCs with MEA showed that nearby neurons often fired synchronously, with spike delays mostly within 1 ms range. This synchronized firing - narrow correlation - was blocked by gap junction blocker, heptanol, but not by glutamatergic synapse blocker, kynurenic acid. By tracking down all the RGC pairs which showed narrow correlation, we could harvest 40 functional connectivity maps of RGCs which showed the cell cluster firing together. We suggest that finding functional connectivity map would be useful in stimulation encoding strategy for the retinal prosthesis since stimulating the cluster of RGCs would be more efficient than separately stimulating each individual RGC.

Kynurenic acid as an additional endogenous anti-aggregatory factor

Kynurenic acid [KNA] is an endogenous metabolite of tryptophan that has been characterized both in the brain and various peripheral organs that included blood vessels, kidneys, hearts, intestine and the eye. Its release from the vascular tissues which also release prostacyclin and nitric oxide directed us to investigate its influence on platelets aggregation. Exposure of guinea-pig platelets to KNA in concentrations ranging from 0.1 to 2mM inhibited adenosine diphosphate [ADP] and arachidonic acid [AA] induced aggregations in a dose-dependent manner.The inhibitory dose 50 values against ADP and AA were found to be 1.1 +/- 0.06 and 0.9 +/- 0.08 mM respectively. [N=8]. The anti-aggregatory effect was significantly reversed in presence of exogenous Ca[2+]. Elevation of the level of the plasma by 0.5mM Ca[2+] reversed the anti-aggregatory effect KNA by 60 +/- 4.5 and 71.5 +/- 6.3% against ADP and AA, respectively [P<0.01, N=8]. It is suggested that KNA may be considered as an additional endogenous anti-aggregatory factor

Role of glutamate receptors in the spiral ganglion neuron damage induced by acoustic noise / 生理学报

The aim of the present study was to investigate the role of glutamate receptors in the damage of spiral ganglion neurons (SGNs) induced by acute acoustic noise. This investigation included in vivo and in vitro studies. In vivo, kynurenic acid (KYNA), a broad-spectrum antagonist of glutamate receptors, was applied to the round window of guinea pigs, and its protective effect was observed. The animals were divided into three groups: control (saline, 0.9%, 10 microL), saline (0.9%, 10 microL) + noise and KYNA (5 mmol/L, 10 microL) + noise. Saline and KYNA were applied to the round window membrane with a microsyringe. The animals were exposed to 110 dB SPL of white noise for 1 h. Hearing thresholds for auditory brainstem responses (ABRs) and compound action potentials (CAPs) in all animals were measured before and after treatment. The amplitudes of III waveform of ABR and N1 waveform of CAP and the latency of N1 waveform at different stimulation levels (intensity-amplitude and intensity-latency functions) were also measured. The cochleas were then dissected for transmission electron microscopy (TEM) after final electrophysiological measurement. In vitro, the SGNs of the normal guinea pigs were isolated and glutamate (100 micromol/L or 1 000 micromol/L) was added into the medium. The morphology of the SGNs was examined by light microscopy. In vivo results showed that the hearing function and morphology of the inner ear including hair cells and SGNs in the control group were normal. Compared with that in the control group the thresholds for ABR and CAP (click and tone burst) in saline + noise group were elevated significantly. The input-output functions showed that the amplitudes of III waveform of ABR and N1 waveform of CAP decreased and the latency of N1 waveform increased obviously. There was significant difference in the amplitude and latency between saline + noise group and KYNA + noise group (P<0.05). TEM indicated obvious swelling and vacuoles at the terminate of dendrites of SGNs in NS + noise group. On the contrary, the afferent dendrites in KYNA + noise group showed normal appearance without swelling and vacuoles. In vitro experiment showed that the isolated SGNs of guinea pigs obviously swelled and even died after application of 100 micromol/L or 1 000 micromol/L glutamate. These results suggest that noise exposure causes hearing impairment, damage of hair cells and hair cell/afferent synapse and death of SGNs. The antagonist of glutamate receptors provides protective effects against hearing loss and SGN damage. It is inferred that excessive release of glutamate from the inner hair cells induced by noise may be responsible for these damages. Glutamate receptors are involved in the degeneration and death of SGNs.

Glutamatergic neurotransmission modulates hypoxia-induced hyperventilation but not anapyrexia

The interaction between pulmonary ventilation (V E) and body temperature (Tb) is essential for O2 delivery to match metabolic rate under varying states of metabolic demand. Hypoxia causes hyperventilation and anapyrexia (a regulated drop in Tb), but the neurotransmitters responsible for this interaction are not well known. Since L-glutamate is released centrally in response to peripheral chemoreceptor stimulation and glutamatergic receptors are spread in the central nervous system we tested the hypothesis that central L-glutamate mediates the ventilatory and thermal responses to hypoxia. We measured V E and Tb in 40 adult male Wistar rats (270 to 300 g) before and after intracerebroventricular injection of kynurenic acid (KYN, an ionotropic glutamatergic receptor antagonist), alpha-methyl-4-carboxyphenylglycine (MCPG, a metabotropic glutamatergic receptor antagonist) or vehicle (saline), followed by a 1-h period of hypoxia (7 percent inspired O2) or normoxia (humidified room air). Under normoxia, KYN (N = 5) or MCPG (N = 8) treatment did not affect V E or Tb compared to saline (N = 6). KYN and MCPG injection caused a decrease in hypoxia-induced hyperventilation (595 ± 49 for KYN, N = 7 and 525 ± 84 ml kg-1 min-1 for MCPG, N = 6; P < 0.05) but did not affect anapyrexia (35.3 ± 0.2 for KYN and 34.7 ± 0.4ºC for MCPG) compared to saline (912 ± 110 ml kg-1 min-1 and 34.8 ± 0.2ºC, N = 8). We conclude that glutamatergic receptors are involved in hypoxic hyperventilation but do not affect anapyrexia, indicating that L-glutamate is not a common mediator of this interaction.

A Neurodegenerative Hypothesis of Cytokine-Serotonin Interaction in Major Depression / 신경정신의학

A growing body of evidence suggests that major depression is associated with increased productions of pro-inflammatory cytokines such as IL-1, IL-6, IL-12 or TNF-alpha and increased concentrations of prostaglandin E2 and negative-regulatory cytokines such as IL-4 or IL-10. In major depression, interactions among brain 5-HT levels, the activity of its autoreceptors, and that of postsynaptic receptors play a critical role in mood changes and depression. Recently, the link between cytokines and serotonergic turnover has been explored. Cytokines such as IL-1, IL-2 and IFN-gamma reduce the production of 5-HT by stimulating the activity of indoleamine-2,3 dioxygenase (IDO), an enzyme which convert tryptophan, the precursor of 5-HT to kynurenine. The kynurenine is metabolized into quinolinic acid (quinolinate) and kynurenic acid (kynurenate), an excitotoxic NMDA receptor agonist and the antagonist of three ionotropic excitotatory aminoacid receptors, respectively. The cytokineserotonin interaction through IDO that leads to the challenge between quinolinate and kynurenate in the brain may finally induce the neurodegeneration in depression. The neurodegeneration hypothesis of depression can explain how people cope with psychological or physical stress at different stages according to severity and duration of stress and why major depression develops.

Changes in Vestibular Nerve Activity Following Acute Hypotension in Rats

The basic mechanism for the excitation of the peripheral vestibular receptors following acute hypotension induced by sodium nitroprusside (SNP) or hemorrhage was investigated in anesthetized rats. Electrical activity of the afferent vestibular nerve was measured after pretreatment with kynurenic acid, an NMDA receptor antagonist. The activity of the vestibular nerve at rest following acute hypotension induced by SNP or simulating hemorrhage was a greater increase than in control animals. The gain of the vestibular nerve with sinusoidal rotation following acute hypotension increased significantly compared to control animals. The acute hypotension induced by SNP or hemorrhage did not change the activity of the afferent vestibular nerve after kynurenic acid injection. These results suggest that acute hypotension produced excitation of the vestibular hair cells via glutamate excitotoxicity in response to ischemia.

Excitatory amino acid receptor blockade within the caudal pressor area and rostral ventrolateral medulla alters cardiovascular responses to nucleus raphe obscurus stimulation in rats

Pressor responses elicited by stimulation of the nucleus raphe obscurus (NRO) depend on the integrity of the rostral ventrolateral medulla (RVLM). Therefore, to test the participation of excitatory amino acid (EAA) receptors in the cardiovascular responses evoked by NRO stimulation (1 ms, 100 Hz, 40-70 æA, for 10 s), the EAA antagonist kynurenic acid (Kyn) was microinjected at different sites in the ventrolateral medullar surface (2.7 nmol/200 nl) of male Wistar rats (270-320 g, N = 39) and NRO stimulation was repeated. The effects of NRO stimulation were: hypertension (deltaMAP = +43 ± 1 mmHg, P<0.01), bradycardia (deltaHR = -30 ± 7 bpm, P<0.01) and apnea. Bilateral microinjection of Kyn into the RVLM, which did not change baseline parameters, almost abolished the bradycardia induced by NRO stimulation (deltaHR = -61 ± 3 before vs -2 ± 3 bpm after Kyn, P<0.01, N = 7). Unilateral microinjection of Kyn into the CVLM did not change baseline parameters or reduce the pressor response to NRO stimulation (deltaMAP = +46 ± 5 before vs +48 ± 5 mmHg after Kyn, N = 6). Kyn bilaterally microinjected into the caudal pressor area reduced blood pressure and heart rate and almost abolished the pressor response to NRO stimulation (deltaMAP = +46 ± 4 mmHg before vs +4 ± 2 mmHg after Kyn, P<0.01, N = 7). These results indicate that EAA receptors on the medullary ventrolateral surface play a role in the modulation of the cardiovascular responses induced by NRO stimulation, and also suggest that the RVLM participates in the modulation of heart rate responses and that the caudal pressor area modulates the pressor response following NRO stimulation

Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport) in the plasma of these patients. Concentration of digoxin, a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine) and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.

Respiratory effects of kynurenic acid microinjected into the ventromedullary surface of the rat

Several studies demonstrate that, within the ventral medullary surface (VMS), excitatory amino acids are necessary components of the neural circuits involved in the tonic and reflex control of respiration and circulation. In the present study we investigated the cardiorespiratory effects of unilateral microinjections of the broad spectrum glutamate antagonist kynurenic acid (2 nmol/200 nl) along the VMS of urethane-anesthetized rats. Within the VMS only one region was responsive to this drug. This area includes most of the intermediate respiratory area, partially overlapping the rostral ventrolateral medulla (IA/RVL). When microinjected into the IA/RVL, kynurenic acid produced a respiratory depression, without changes in mean arterial pressure or heart rate. The respiratory depression observed was characterized by a decrease in ventilation, tidal volume and mean inspiratory flow and an increase in respiratory frequency. Therefore, the observed respiratory depression was entirely due to a reduction in the inspiratory drive. Microinjections of vehicle (200 nl of saline) into this area produced no significant changes in breathing pattern, blood pressure or heart rate. Respiratory depression in response to the blockade of glutamatergic receptors inside the rostral VMS suggests that neurons at this site have an endogenous glutamatergic input controlling the respiratory cycle duration and the inspiratory drive transmission.

Effects of glutamate receptor antagonists and protein synthesis inhibitor on delayed neuronal death induced by transient global ischemia in rat brain

It has been well documented that transient forebrain global ischemia causes selective neuronal degeneration in hippocampal CA1 pyramidal neurons with a delay of a few days. The mechanism of this delayed hippocampal CA1 pyramidal neuronal death (DND) is still controversial. To delineate the mechanisms of the DND, the effects of treatment with MK-801, an NMDA receptor antagonist, kynurenic acid, a NMDA/non-NMDA receptor antagonist, and/or cycloheximide, a protein synthesis inhibitor, on the DND were investigated in male Wistar rats. To examine the participation of apoptotic neuronal death in the DND, TUNEL staining was performed in ischemic brain section. Global ischemia was induced by 4-vessel occlusion for 20 min. All animals in this study showed the DND 3 and 7 days after the ischemic insult. The DND that occurred 3 days and 7 days after the ischemia were not affected by pretreatment with MK-801 (I mg/kg), but markedly attenuated by the pretreatment with kynurenic acid (500 mg/kg). Treatment with cycloheximide (1 mg/kg) also markedly inhibited the DND. The magnitudes of attenuation by the two drugs were similar. The magnitude of attenuation by co-treatments with kynurenic acid and cycloheximide was not greater than that with any single treatment. TUNEL staining was negative in the sections obtained 1 or 2 days after the ischemic insults, but it was positive at hippocampal CA1 pyramidal cells in sections collected 3 days after the ischemia. These results suggested that the DND should be mediated by the activation of non-NMDA receptor, not by the activation of NMDA receptor and that the activation of AMPA receptor should induce the apoptotic process in the DND.

The Effects of N-Methyl_D-Aspartic Acid, and Antagonism by Kynurenic Acid on Neurons in the Cathish Retina

To investigate the mechanism of the excitatory signal transmission, the effects of N-methyl-D-aspartate(NMDA, ionotropic glutamate agonist) and kynurenic acid(glutamate antagonist) on catfish retinal neurons were explored using conventional intracellular recording techniques. Horizontal cells were depolarized by glutamate, kainate, quisqualate, and NMDA but gyperpolarized by kynurenate. Transient components of both ON-and OFF-bipolar cells were reduced either by glutamate or by NMDA. Kynurenate suppressed sustained components of the third-order neurons or OFF-bipolar cells. Furthermore, kynurenate blocked the depolarizing actions of NMDA on horizontal cells and ON-sustained cells with large ON-transient components. The results suggest that NMDA would exert a tonic depolarization in the horizontal cells and the 3rd-order neurons, and there might be a preferential suppression on the a NMDA receptors by kynurenic acid in the catfish retina.

Putative pathways involved in cardiovascular responses evoked from the caudal pressor area

1. The caudal pressor area (CPA) is a recently identified site within the ventrolateral medulla which is involved in cardiovascular regulation. CPA chemical stimulation by L-glutamate produces an increase in arterial blood pressure (ABP) while its inhibition by GABA or glycine evokes marked hypotension. In the present study, we sought to determine the potential neural pathways underlyng these responses. 2. In urethane-anesthetized, paralyzed, artificially ventilated rats, CPA inhibition by bilateral microinjection of the inhibitory amino acid glycine (Gly, 100 nmol 200 nl-1 site-1) produced an average decrease of -38 + or - 4.3 mmHg in ABP (n = 6). Ten min after bilateral microinjection of the broad-spectrum glutamate antagonist kynurenic acid (KYN, 2 nmol 200 nl-1 site-1) into the cauldal ventrolateral medulla (CVLM) depressor responses to CPA inhibition were virtually abolished (-3 + or - 1.7 mmHg, P<0.05). Similar microinjection of KYN into the rostral ventrolateral medulla (RVLM) or into the CPA itself did not modify depressor responses to CPA inhibiton by glycine. 3. CPA stimulation by bilateral microinjection of the excitatory amino acid L-glutamate (L-glu, 50 nmol 200 nl-1 site-1) produced an increase in ABP (+43 + or - 5.4 mmHg, N= 6). Bilateral microinjection of the GABA A antagonist bicuculline methiodide (BIC, 200 pmol 200 nl-1 site-1) into the CVLM markedly reduced pressor responses to CPA stimulation (+6 + or - 2.7 mmHg, P<0.05). Similar application of BIC into the RVLM or CPA did not modify pressor responses to CPA stimulation by glutamic acid

The structural change of rat cerebral cortex by the in situ perfusion with L-glutamate, glycine and kynurenate / 대한해부학회지

No abstract available.