Osmotic stimulation of vasopressin mRNA content in the supraoptic nucleus requires synaptic activation

1995 ◽  
Vol 268 (4) ◽  
pp. R1034-R1039 ◽  
Author(s):  
C. D. Sladek ◽  
K. Y. Fisher ◽  
H. E. Sidorowicz ◽  
J. R. Mathiasen
Keyword(s):  
Synaptic Input ◽  
Supraoptic Nucleus ◽  
Kynurenic Acid ◽  
Excitatory Amino Acid ◽  
Vasopressin Release ◽  
Amino Acid Receptors ◽  
Mrna Content ◽  
Supraoptic Neurons ◽  
Vasopressin Neurons

The role of synaptic input to the vasopressin neurons in hypertonicity-induced increase in vasopressin mRNA content was evaluated. Synaptic connection with the anterior hypothalamus is required for hypertonicity to increase vasopressin release. However, the potential for other mechanisms to induce the increase in vasopressin mRNA content is suggested by the fact that hypertonicity induces depolarization of supraoptic neurons independently of synaptic input. Explants of the hypothalamoneurohypophysial system were used to study the effect of depolarization and hypertonicity in the presence and absence of nonspecific synaptic blockade by 15 mM MgSO4 or blockade of excitatory amino acid receptors with kynurenic acid. Vasopressin release and mRNA content were increased by depolarization with 40 mM KCl and by exposure to hypertonicity (P < 0.05). Basal and osmotically stimulated vasopressin release was decreased by MgSO4 and by kynurenic acid. Both agents prevented the hypertonicity-induced increase in vasopressin mRNA content. Thus either synaptic input or increased VP release is required for hypertonicity to increase vasopressin mRNA, and excitatory amino acids are implicated in this response.

Role of Tryptophan-kynurenine Pathway in Depression: Psychopathological Aspect

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
A.-M. Myint
Keyword(s):  
Kynurenic Acid ◽  
Excitatory Amino Acid ◽  
Kynurenine Pathway ◽  
Response To Treatment ◽  
Excitatory Amino Acid Receptors ◽  
Amino Acid Receptors ◽  
Tryptophan Catabolism ◽  
Ifn Γ ◽  
The Brain

It was reported that cytokines such as IFN-γ reduce the synthesis of 5-HT by stimulating the activity of indoleamine 2,3 dioxygenase (IDO) enzyme which degrades tryptophan to kynurenine. Kynurenine is further metabolized to kynurenic acid (KYNA), 3-hydroxykynurenine (3OHK) and quinolinic acid (QA) by kynurenine aminotransferase (KAT), kynurenine 3-monooxygenase (KMO) and kynureninase. Both KMO and kynureninase are also shown to be activated by IFNγ. The 3OHK is neurotoxic apoptotic while QA is the excitotoxic N-methyl-D-aspartate (NMDA) receptor agonist. Conversely KYNA is an antagonist of all three ionotropic excitatory amino acid receptors and considered neuroprotective. In the brain, tryptophan catabolism occurs in the astrocytes and. The astrocytes are shown to produce mainly KYNA whereas microglia and macrophages produced mainly 3OHK and QA. The astrocytes have been demonstrated to metabolise the QA produced by the neighbouring microglia.Tryptophan breakdown has been found to be increased but KYNA, the neuroprotective metabolite is decreased in both blood and cerebrospinal fluid of the patients with major depression compared to healthy controls. Moreover, the ratio between KYNA and 3OHK showed significant correlation with response to treatment. These findings lead to the hypothesis an imbalance neuroprotection-neurodegener-ation in terms of kynurenine metabolites and their immunological and biochemical interactions in the brain might further induce the apoptosis of the neuroprotective astrocytes and the vulnerability to stress is thereby enhanced.

scholarly journals Circulating Secretin Activates Supraoptic Nucleus Oxytocin and Vasopressin Neurons via Noradrenergic Pathways in the Rat

Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2681-2688 ◽  
Author(s):  
Sathya Velmurugan ◽  
Paula J. Brunton ◽  
Gareth Leng ◽  
John A. Russell
Keyword(s):  
Amino Acid ◽  
Firing Rate ◽  
Noradrenaline Release ◽  
Supraoptic Nucleus ◽  
Female Rats ◽  
Adrenoceptor Antagonist ◽  
Intracerebroventricular Infusion ◽  
Neuroendocrine Neurons ◽  
Vasopressin Neurons

Secretin is a 27-amino acid brain-gut peptide from duodenal S-cells. We tested the effects of systemic administration of secretin to simulate its postprandial release on neuroendocrine neurons of the supraoptic nucleus (SON) in urethane-anesthetized female rats. Secretin dose-dependently increased the firing rate of oxytocin neurons, more potently than cholecystokinin, and dose-dependently increased plasma oxytocin concentration. The effect of secretin on SON vasopressin neurons was also predominantly excitatory, in contrast to the inhibitory actions of cholecystokinin. To explore the involvement of noradrenergic inputs in secretin-induced excitation, benoxathian, an α1-adrenoceptor antagonist, was infused intracerebroventricularly. Benoxathian intracerebroventricular infusion blocked the excitation by secretin of both oxytocin and vasopressin neurons. To test the role of local noradrenaline release in the SON, benoxathian was microdialyzed onto the SON. The basal firing rate of oxytocin neurons was slightly reduced and the secretin-induced excitation was attenuated during benoxathian microdialysis. Hence, noradrenergic pathways mediate the excitation by systemic secretin of oxytocin neurons via α1-adrenoceptors in the SON. As both systemic secretin and oxytocin are involved in regulating gastrointestinal functions and natriuresis, systemically released secretin might act partly through oxytocin.

Mechanisms of pressor and bradycardic responses to L-glutamate microinjected into the NTS of conscious rats

1994 ◽  
Vol 266 (3) ◽  
pp. R730-R738 ◽  
Author(s):  
E. Colombari ◽  
L. G. Bonagamba ◽  
B. H. Machado
Keyword(s):  
Amino Acid ◽  
Kynurenic Acid ◽  
Excitatory Amino Acid ◽  
Pressor Response ◽  
Excitatory Amino Acid Receptors ◽  
Amino Acid Receptors ◽  
Conscious Rats ◽  
Reflex Bradycardia ◽  
Autonomic Pathways ◽  
Related Pattern

Microinjection of increasing doses of L-glutamate (L-Glu, 0.03-5.0 nmol/100 nl) into the nucleus tractus solitarii (NTS) produced a dose-related pressor and bradycardic response. Prazosin virtually abolished the pressor response but produced no changes in the bradycardic response to L-Glu, indicating that bradycardia is not reflex in origin. The bradycardic response was blocked by atropine. In three different groups of rats, excitatory amino acid receptors in the NTS were blocked by increasing doses of kynurenic acid (0.5, 2.0, and 10.0 nmol/100 nl) and the pressor and bradycardic responses to L-Glu (1 nmol/100 nl) were reduced in a dose-related pattern. Reflex bradycardia induced by an increase in pressure caused by phenylephrine (iv) was also blocked by kynurenic acid. These data show that microinjection of L-Glu into the NTS of conscious rats produced pressor and bradycardic responses, which are due to the activation of two independent autonomic pathways. The data also indicate that the activation of both pathways is mediated by excitatory amino acid receptors. Considering that reflex bradycardia was also blocked by kynurenic acid, we suggest that L-Glu and excitatory amino acid receptors are part of the parasympathetic limb of the baroreceptor reflex. The pressor response to L-Glu is also mediated by excitatory amino acid receptors, but its physiological meaning is still unclear.

Kynurenic acid distribution into brain and peripheral tissues of mice

1994 ◽  
Vol 72 (2) ◽  
pp. 161-167 ◽  
Author(s):  
G. L. Lou ◽  
C. Pinsky ◽  
D. S. Sitar
Keyword(s):  
Amino Acid ◽  
Tissue Distribution ◽  
Kynurenic Acid ◽  
Liquid Scintillation ◽  
Excitatory Amino Acid ◽  
Scintillation Counting ◽  
Excitatory Amino Acid Receptors ◽  
Peripheral Tissues ◽  
Amino Acid Receptors ◽  
Acid Toxicity

Kynurenic acid (KYN), an antagonist of excitatory amino acid receptors, is a putative antidote against neuroexcitatory amino acid toxicity. We studied various doses (0.05–3.17 mmol/kg, i.p.) and the effects of probenecid coadministration (0.70 mmol/kg, i.p.) on tissue distribution of KYN in male and female Swiss–Webster mice. After injection of [3H]KYN, samples of brain, heart, liver, kidney, skeletal muscle, and gut were collected at selected times and assayed for KYN by liquid scintillation counting. The substance was absorbed rapidly and distributed into all tissues. Its content (nmol/g, mean ± SE) at 60 min was 0.26 ± 0.05, 1.80 ± 0.05, and 40.4 ± 8.1 in brain (for 0.05, 0.53, and 3.17 mmol/kg), 1.43 ± 0.11, 14.3 ± 3.7, and 212 ± 32 in heart, 1.16 ± 0.21, 10.6 ± 2.6, and 254 ± 21 in liver, and 7.41 ± 2.65, 180 ± 63, and 1899 ± 254 in kidney. Net accumulation of KYN in brain was much lower than in other tissues. Probenecid increased KYN concentration in brain 2.5-fold. Peak brain:blood concentration ratio occurred between 60 and 180 min, was inversely associated with dose, and was not affected by probenecid. Although brain content was similar, female mice had an earlier peak brain:blood ratio (120 min) than males (180 min) for the 0.05 mmol/kg dose. Our results suggest the presence of a restricted transfer process for KYN with delayed egress from brain.Key words: kynurenic acid, brain, tissue distribution.

ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and P2Y purinergic receptors

2007 ◽  
Vol 292 (1) ◽  
pp. R423-R431 ◽  
Author(s):  
Zhilin Song ◽  
Sukumar Vijayaraghavan ◽  
Celia D. Sladek
Keyword(s):  
Intracellular Calcium ◽  
Supraoptic Nucleus ◽  
Purinergic Receptors ◽  
Calcium Concentration ◽  
Pyridoxal Phosphate ◽  
Combined Treatment ◽  
Vasopressin Release ◽  
Intracellular Ca ◽  
Disulphonic Acid ◽  
Supraoptic Neurons

ATP increases intracellular calcium concentration ([Ca2+]i) in supraoptic nucleus (SON) neurons in hypothalamo-neurohypophyseal system explants loaded with the Ca2+-sensitive dye, fura 2-AM. Involvement of P2X purinergic receptors (P2XR) in this response was anticipated, because ATP stimulation of vasopressin release from hypothalamo-neurohypophyseal system explants required activation of P2XRs, and activation of P2XRs induced an increase in [Ca2+]i in dissociated SON neurons. However, the ATP-induced increase in [Ca2+]i persisted after removal of Ca2+ from the perifusate ([Ca2+]o). This suggested involvement of P2Y purinergic receptors (P2YR), because P2YRs induce Ca2+ release from intracellular stores, whereas P2XRs are Ca2+-permeable ion channels. Depletion of [Ca2+]i stores with thapsigargin (TG) prevented the ATP-induced increase in [Ca2+]i in zero, but not in 2 mM [Ca2+]o, indicating that both Ca2+ influx and release of intracellular Ca2+ contribute to the ATP response. Ca2+ influx was partially blocked by cadmium, indicating a contribution of voltage-gated Ca2+ channels. PPADS (pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid), and iso-PPADS, P2XR antagonists, attenuated, but did not abolish, the ATP-induced increase in [Ca2+]i. Combined treatment with PPADS or iso-PPADS and TG prevented the response. A cocktail of P2YR agonists consisting of UTP, UDP, and 2-methylthio-ADP increased [Ca2+]i (with or without tetrodotoxin) that was markedly attenuated by TG. 2-Methylthio-ADP alone induced consistent and larger increases in [Ca2+]i than UTP or UDP. MRS2179, a specific P2Y1R antagonist, eliminated the response to ATP in zero [Ca2+]o. Thus, both P2XR and P2YR participate in the ATP-induced increase in [Ca2+]i, and the P2Y1R subtype is more prominent than P2Y2R, P2Y4R, or P2Y6R in SON.

scholarly journals Protective effects of glucosamine-kynurenic acid after compression-induced spinal cord injury in the rat

2012 ◽  
Vol 7 (6) ◽  
pp. 996-1004 ◽  
Author(s):  
Andrea Korimová ◽  
Dáša Cížková ◽  
Jozsef Toldi ◽  
László Vécsei ◽  
Ivo Vanický
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Amino Acid ◽  
Kynurenic Acid ◽  
Excitatory Amino Acid ◽  
Protective Effects ◽  
Tissue Destruction ◽  
Amino Acid Receptors ◽  
Cord Injury ◽  
Secondary Tissue

AbstractKynurenic acid (KYNA), a metabolite of the essential amino acid L-tryptophan, is a broad spectrum antagonist of excitatory amino acid receptors, which have also anticonvulsant and neuroprotective properties. After spinal cord injury (SCI), excitotoxicity is considered to play a significant role in the processes of secondary tissue destruction in both grey and white matter of the spinal cord. In this study, we have tested the potential therapeutic effect of glucosamine-kynurenic acid, administered after experimental compression-induced SCI in the rat. Spinal application of glucosamine-kynurenic acid continually for 24 hr after experimental SCI resulted in improved motor function recovery, beginning from the first week of evaluation and continuing until the end of the study (4 weeks). After 4 weeks’ survival, quantitative morphometric analysis of the spinal cord showed that glucosamine-kynurenic acid treatment was associated with improved tissue preservation at the lesion site. These findings indicate that spinal application of glucosaminekynurenic acid is neuroprotective and improves the outcome even when administered after spinal trauma. Our results suggest that the treatments initiated in early posttraumatic period can alleviate secondary injury and improve the final outcome after SCI.

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