The Experts below are selected from a list of 42849 Experts worldwide ranked by ideXlab platform
Takao Kubo - One of the best experts on this subject based on the ideXlab platform.
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Excitatory Amino Acid Receptors in the Paraventricular Hypothalamic Nucleus Mediate Pressor Response Induced by Carotid Body Chemoreceptor Stimulation in Rats
Clinical and experimental hypertension (New York N.Y. : 1993), 1997Co-Authors: Takao Kubo, Y. Yanagihara, H. Yamaguchi, R. FukumoriAbstract:In urethane-anesthetized rats with spinal transection, antagonists of excitatory Amino Acid Receptors, P2 purinoceptors and adrenoceptors were microinjected into the paraventricular hypothalamic nucleus (PVN) and their effects on the pressor response evoked by carotid body chemoreceptor stimulation were examined. Microinjections of the non-selective excitatory Amino Acid antagonist kynurenate, the non-NMDA receptor antagonist CNQX and the NMDA antagonist 2-Amino-5-phosphonovalerate (AP5) into the PVN inhibited the chemoreceptor reflex-induced pressor response. The excitatory Amino Acid agonist L-glutamate injected into the PVN produced an increase in blood pressure. The P2 purinoceptor antagonist suramin did not affect the pressor response and ATP did not affect basal blood pressure. The alpha adrenoceptor antagonist phentolamine, prazosin and yohimbine also inhibited the chemoreceptor-induced pressor response, while the beta antagonist propranolol did not affect it. These findings indicate that excitatory Amino Acid Receptors and alpha adrenoceptors in the PVN are involved in mediating the pressor response induced by carotid body chemoreceptor stimulation in rats.
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Excitatory Amino Acid Receptors in the rostral ventrolateral medulla mediate hypertension induced by carotid body chemoreceptor stimulation
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994Co-Authors: Motoaki Amano, Tetsuya Asari, Takao KuboAbstract:The rostral ventrolateral medulla (RVLM) is involved in the mediation of cardiovascular responses to peripheral chemoreceptor stimulation. To investigate whether excitatory Amino Acid inputs in the RVLM are related to the responses to chemoreceptor stimulation, we microinjected kynurenate, an Amino Acid antagonist, unilaterally into the RVLM and examined its effects on the pressor response to stimulation of carotid body chemoReceptors. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. The carotid chemoReceptors were stimulated with isotonic solutions of inorganic phosphate solution. Stimulation of carotid body chemoReceptors produced increases in blood pressure. Kynurenate injected ipsilaterally but not contralaterally into the RVLM markedly inhibited the pressor response to chemoreceptor stimulation. In rats with spinal transection, stimulation of carotid body chemoReceptors also produced increases in blood pressure. The pressor response in rats with spinal transection was inhibited by intravenous injection of a vasopressin antagonist or by kynurenate injected ipsilaterally into the RVLM. Kynurenate injected into the RVLM inhibited the pressor response to NMDA, AMPA and kainate but not to acetylcholine in intact rats. These findings indicate that excitatory Amino Acid Receptors are involved in mediating the pressor response to carotid body chemoreceptor stimulation in the rat RVLM. It appears that the chemoreceptor stimulation produces an increase in vasopressin release and the enhancement of vasopressin release is also mediated by an increase in excitatory Amino Acid inputs in the RVLM.
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Ipsilateral but not contralateral blockade of excitatory Amino Acid Receptors in the caudal ventrolateral medulla inhibits aortic baroreceptor reflex in rats
Naunyn-Schmiedeberg's archives of pharmacology, 1991Co-Authors: Takao Kubo, M. Kihara, Yoshimi MisuAbstract:The caudal ventrolateral medulla (CVLM) contains vasodepressor neurons which, when activated, decrease vasomotor tone. To investigate whether excitatory Amino Acid Receptors in the CVLM of the rat are involved in mediation of the aortic baroreceptor reflex, we microinjected Amino Acid antagonists unilaterally into the CVLM and examined their effects on the depressor response to electrical stimulation of the aortic nerve which contains mainly baroreceptor afferent fibers in rats. Male Wistar rats were anaesthetized with urethane, paralyzed and artificially ventilated. To block reflex vagal effects, methylatropine (1 mg/kg) was given intravenously. Kynurenate (227 ng), an excitatory Amino Acid antagonist, injected ipsilaterally but not contralaterally into the CVLM markedly inhibited the depressor response to aortic nerve stimulation, while both injections produced a similar small increase in basal blood pressure. Muscimol (1 ng), a GABA receptor agonist, injected ipsilaterally into the CVLM partly inhibited the baroreflex response, while it produced a moderate increase in basal blood pressure. 2-Amino-5-phosphonovalerate (APV) (10 ng), a N-methyl-d-aspartate (NMDA) receptor antagonist, and MK-801 (30 ng), a NMDA receptor channel blocker, partly inhibited the baroreflex response. MK-801 (30 ng) injected into the CVLM reduced the depressor response to the NMDA receptor agonist NMDA (0.3 ng) but not to the quisqualate receptor agonist quisqualate (0.1 ng) and the kainate receptor agonist kainate (0.1 ng), while kynurenate (227 ng) inhibited the depressor response to all three excitatory Amino Acid receptor agonists. These findings provide further evidence for the presence of excitatory Amino Acid Receptors involved in mediating the aortic baroreceptor reflex in the rat CVLM. It appears that neurons other than the vasodepressor neurons in the CVLM, at least in part, play a role in transmitting the aortic baroreceptor reflex. In addition, both NMDA and non-NMDA Receptors may be responsible for the mediation of the reflex.
Darryle D. Schoepp - One of the best experts on this subject based on the ideXlab platform.
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synthesis and pharmacological characterization of l trans 4 tetrazolylproline ly300020 a novel systemically active ampa receptor agonist
Bioorganic & Medicinal Chemistry Letters, 1993Co-Authors: James A Monn, Matthew John Valli, Rebecca A True, David J Leander, Darryle D. Schoepp, David M LodgeAbstract:LY300020, a conformationally constrained, ω-tetrazole-containing analog of L-glutamic Acid was prepared and has been shown to be a relatively potent, highly selective, systemically- active AMPA receptor agonist. The activity of LY300020 was shown to be highly stereoselective as its enantiomer, LY301900, was devoid of binding affinity at ionotropic excitatory Amino Acid Receptors.
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The metabotropic excitatory Amino Acid receptor agonist 1S,3R-ACPD selectively potentiates N-methyl-D-aspartate-induced brain injury.
European journal of pharmacology, 1992Co-Authors: John W Mcdonald, Darryle D. SchoeppAbstract:Abstract The role of metabotropic type excitatory Amino Acid Receptors in brain injury was assessed using the selective metabotropic receptor agonist, (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic Acid (1S,3R-ACPD). Intrastriatal stereotaxic injection of 1S,3R-ACPD (250 nmol) in PND 7 rats produced little brain injury as assessed by hemispheric weight disparities. However, 1S,3R-ACPD markedly potentiated N-methyl-D-aspartate (NMDA)-, but not α-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic Acid (AMPA)-, mediated brain injury. This effect was stereoselective since the inactive metabotropic agonist, 1R,3S-ACPD, did not potentiate NMDA toxicity.
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activation of hippocampal metabotropic excitatory Amino Acid Receptors leads to seizures and neuronal damage
Neuroscience Letters, 1992Co-Authors: Aida I Sacaan, Darryle D. SchoeppAbstract:A role for ionotropic (NMDA, AMPA, and kainate) excitatory Amino Acid (EAA) Receptors in seizure and seizure-related brain damage is well documented. To study the possible role of metabotropic (G-protein linked) EAA Receptors in this regard, a highly selective metabotropic EAA agonist was injected into the hippocampus of halothane-anesthetized rats. This resulted in delayed-onset seizures and selective hippocampal neuronal damage that was indirectly mediated by NMDA Receptors. This provides direct evidence for a novel role of metabotropic EAA Receptors in the etiology of seizures and neuronal damage.
Glenn M Toney - One of the best experts on this subject based on the ideXlab platform.
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sympathoexcitation by pvn injected bicuculline requires activation of excitatory Amino Acid Receptors
Hypertension, 2003Co-Authors: Qing Hui Chen, Joseph R Haywood, Glenn M ToneyAbstract:Acute blockade of γ-Aminobutyric Acid (GABA)-A Receptors in the hypothalamic paraventricular nucleus (PVN) increases mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve activity (SNA). However, the underlying neural mechanisms have not been fully determined. We tested the hypothesis that responses to GABA-A receptor blockade in the PVN require activation of local ionotropic excitatory Amino Acid (EAA) Receptors. MAP, HR, and renal SNA responses to unilateral PVN microinjection of bicuculline methobromide (BIC, 0.1 nmol) were recorded before and after ipsilateral PVN injection of either vehicle (saline), the nonselective ionotropic EAA receptor antagonist kynurenate (KYN), the NMDA receptor antagonist D(-)-2-Amino-5-phosphonopentanoic Acid (AP5), or the non-NMDA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium (NBQX). Responses to PVN-injected BIC were unaltered by vehicle injection. In contrast, injection of KYN (7.2 nmol; n=4) nearly abolished ABP and renal SNA responses to BIC ( P P P P
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sympathoexcitation by pvn injected bicuculline requires activation of excitatory Amino Acid Receptors
Hypertension, 2003Co-Authors: Qing Hui Chen, Joseph R Haywood, Glenn M ToneyAbstract:Acute blockade of gamma-Aminobutyric Acid (GABA)-A Receptors in the hypothalamic paraventricular nucleus (PVN) increases mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve activity (SNA). However, the underlying neural mechanisms have not been fully determined. We tested the hypothesis that responses to GABA-A receptor blockade in the PVN require activation of local ionotropic excitatory Amino Acid (EAA) Receptors. MAP, HR, and renal SNA responses to unilateral PVN microinjection of bicuculline methobromide (BIC, 0.1 nmol) were recorded before and after ipsilateral PVN injection of either vehicle (saline), the nonselective ionotropic EAA receptor antagonist kynurenate (KYN), the NMDA receptor antagonist D(-)-2-Amino-5-phosphonopentanoic Acid (AP5), or the non-NMDA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium (NBQX). Responses to PVN-injected BIC were unaltered by vehicle injection. In contrast, injection of KYN (7.2 nmol; n=4) nearly abolished ABP and renal SNA responses to BIC (P<0.01) and significantly attenuated (P<0.05) HR responses as well. Similarly, graded doses of AP5 (0.6, 3, and 6 nmol) and NBQX (0.26, 1.3, and 2.6 nmol) reduced responses to PVN-injected BIC in a dose-related manner, with the 3 nmol (n=7) and 1.3 nmol (n=6) doses producing maximal effects (P<0.05). KYN, AP5, and NBQX did not affect baseline parameters. Effects of a cocktail containing AP5 (3 nmol) and NBQX (1.3 nmol) were greater (P<0.01) than either antagonist alone and were not statistically different from KYN. These data indicate that cardiovascular and renal sympathetic responses to acute GABA-A receptor blockade in the PVN require local actions of EAAs at both NMDA and non-NMDA Receptors.
Jeremy J Lambert - One of the best experts on this subject based on the ideXlab platform.
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General anaesthetic action at transmitter-gated inhibitory Amino Acid Receptors.
Trends in pharmacological sciences, 1999Co-Authors: Delia Belelli, Marco Pistis, John A. Peters, Jeremy J LambertAbstract:Research within the past decade has provided compelling evidence that anaesthetics can act directly as allosteric modulators of transmitter-gated ion channels. Recent comparative studies of the effects of general anaesthetics across a structurally homologous family of inhibitory Amino Acid Receptors that includes mammalian GABAA, glycine and Drosophila RDL GABA Receptors have provided new insights into the structural basis of anaesthetic action at transmitter-gated channels. In this article, the differential effects of general anaesthetics across inhibitory Amino Acid Receptors and the potential relevance of such actions to general anaesthesia will be discussed.
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the actions of propofol on inhibitory Amino Acid Receptors of bovine adrenomedullary chromaffin cells and rodent central neurones
British Journal of Pharmacology, 1991Co-Authors: Tim G Hales, Jeremy J LambertAbstract:1. The interaction of the intravenous general anaesthetic propofol (2,6-diisopropylphenol) with the GABAA receptor has been investigated in voltage-clamped bovine chromaffin cells and rat cortical neurones in cell culture. Additionally, the effects of propofol on the glycine and GABAA Receptors of murine spinal neurones were determined. 2. Propofol (1.7-16.8 microM) reversibly and dose-dependently potentiated the amplitude of membrane currents elicited by GABA (100 microM) applied locally to bovine chromaffin cells. Intracellular application of propofol (16.8 microM) was ineffective. In rat cortical neurones and murine spinal neurones, extracellular application of 8.4 microM and 1.7-16.8 microM propofol respectively produced a potentiation of GABA-evoked currents qualitatively similar to that seen in the bovine chromaffin cell. 3. The potentiation by propofol (1.7 microM) was not associated with a change in the reversal potential of the GABA-evoked whole cell current. On outside-out membrane patches isolated from bovine chromaffin cells, propofol (1.7 microM) had little or no effect on the GABA single channel conductances, but greatly increased the probability of the GABA-gated channel being in the conducting state. 4. The potentiation of GABA-evoked whole cell currents by propofol (1.7 microM) was not influenced by the benzodiazepine antagonist flumazenil (0.3 microM). A concentration of propofol (1.7 microM) that substantially potentiated GABA currents had little effect on currents induced by the activation of the GABAA receptor by pentobarbitone (1 mM). 5. Bath application of propofol (8.4-252 microM), to bovine chromaffin cells voltage clamped at -60 mV, induced an inward current associated with an increase in membrane current noise on all cells sensitive to GABA. Intracellular application of propofol (16.8 microM) was ineffective in this respect. Local application of propofol (600 microM) induced whole cell currents with a reversal potential dependent upon the Cl- gradient across the cell membrane. 6. On outside-out membrane patches formed from bovine chromaffin cells, propofol (30 microM) induced single channels with mean chord conductances of 29 and 12 pS. The frequency of propofol channels was greatly reduced by coapplication of 1 microM bicuculline. Under identical ionic conditions, GABA (1 microM) activated single channels with mean chord conductances of 33, 16 and 10pS. 7. Bath applied propofol (0.84-16.8 microM) dose-dependently potentiated strychnine-sensitive currents evoked by glycine (100 microM) in murine spinal neurones. 8. The relevance of the present results to the general anaesthetic action of propofol is discussed.
J.c. Kolhouse - One of the best experts on this subject based on the ideXlab platform.
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Measurement of Excitatory Sulfur Amino Acids, Cysteine Sulfinic Acid, Cysteic Acid, Homocysteine Sulfinic Acid, and Homocysteic Acid in Serum by Stable Isotope Dilution Gas Chromatography-Mass Spectrometry and Selected Ion Monitoring
Analytical Biochemistry, 1994Co-Authors: C. R. Santhosh-kumar, John C. Deutsch, J.c. Kolhouse, Kathryn L. HassellAbstract:Oxidized sulfur-containing Amino Acids are recognized as agonists of excitatory Amino Acid Receptors in the mammalian nervous system. Homologues of glutamic Acid (homocysteine sulfinic Acid and homocysteic Acid) and aspartic Acid (cysteine sulfinic Acid and cysteic Acid) have been shown to be agonistic to N-methyl-D-aspartate Receptors in animal brain and have been demonstrated in brain tissue. Considerable evidence exists for the role of homocysteic Acid and cysteine sulfinic Acid as endogenous ligands for excitatory Amino Acid Receptors. We report, for the first time, the quantitation of these compounds in normal human serum, by a newly developed gas chromatography-mass spectrometry method that employs stable isotope-dilution selected ion monitoring using internal standards prepared in our laboratory. We also report new methods of synthesis of stable isotope-labeled internal standards used in measuring cysteine sulfinic Acid, cysteic Acid, homocysteine sulfinic Acid, and homocysteic Acid.