The Experts below are selected from a list of 4014 Experts worldwide ranked by ideXlab platform
Thomas E. Salt - One of the best experts on this subject based on the ideXlab platform.
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Contribution of GABAergic inhibition to synaptic responses and LTD early in postnatal development in the rat superior colliculus.
The European journal of neuroscience, 2004Co-Authors: R. Ranney Mize, Thomas E. SaltAbstract:We studied the development of optic tract evoked field potentials (FP) in the rodent superior colliculus (SC) and the effect of GABA Antagonists upon their development and upon induction of long-term depression (LTD). Brain slices were cut from Lister Hooded rats. The optic tract was stimulated while recording from the superficial grey layer. GABAergic inhibition was assessed by adding 100 microm picrotoxin and 3 microm CGP55845 Antagonists to block GABA A,B,C receptors. LTD was induced with a 50 Hz, 20 s tetanus. At age P2, the FP consisted only of a presynaptic spike. The GABA Antagonists had no effect. By P4, the FP consisted of a presynaptic spike, a longer latency population spike, and a field excitatory postsynaptic potential (fEPSP). The fEPSP was slightly prolonged by the GABA Antagonists at this age. By P7-P14, a prominent FP with trailing fEPSP was recorded. The GABA Antagonists usually had a large effect, with the fEPSP increasing in both amplitude and duration. A mature FP was usually recorded in P15-P23 slices where the GABA antagonist effect remained substantial. LTD could be induced in 17 of 30 control slices from rats aged P4-P26. The average fEPSP amplitude after tetanus was 77.9% of control. Pre-treatment with GABA Antagonists produced a short-term potentiation (average 114.0%), rather than LTD, in 14 of 19 cases. This STP was followed by a more prolonged potentiation in 12 of the 14 cases. We conclude that GABAergic inhibitory circuits mature before eye opening and that GABA contributes to induction of LTD in the developing SC.
Francis V. Defeudis - One of the best experts on this subject based on the ideXlab platform.
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Studies on GABA and cardiovascular function using in vivo and in vitro technics
Drug Development Research, 2004Co-Authors: Francis V. DefeudisAbstract:Recent in vivo and in vitro studies regarding the involvement of GABAergic systems in cardiovascular function have been reviewed and analyzed. It seems evident, from studies conducted with various GABA agonists and GABA Antagonists, that activation of central GABAergic systems reduces sympathetic outflow from the hindbrain area of mammals, thereby producing bradycardia and hypotension. As GABA agonists can relax cerebral arteries, blood-borne GABA might also play a role in cerebrovascular regulation. Further research concerning the mechanisms involved in GABA agonist-induced cardiovascular responses could lead to the development of agents that might be effective in treating certain cardiovascular disorders of man, such as hypertension, cerebral atherosclerosis, migraine, and stroke.
T. G. Waldrop - One of the best experts on this subject based on the ideXlab platform.
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Posterior hypothalamic modulation of the respiratory response to CO_2 in cats
Pflügers Archiv, 1991Co-Authors: T. G. WaldropAbstract:Several studies have provided evidence that suprapontine structures are involved in modulating the respiratory response to increases in carbon dioxide. However, the actual neuroanatomical site(s) responsible for this effect has not been identified. Therefore, the purpose of the present study was to determine if the posterior hypothalamus is one rostral site involved in the modulation of the respiratory response to hypercapnia. Phrenic nerve responses to progressive step increases in end-tidal P CO_2 were recorded before and after unilateral microinjection of γ-aminobutyric acid (GABA) Antagonists into the posterior hypothalamus of anesthetized cats, which were paralyzed and ventilated. Microinjection of the Antagonists reduced the apneic threshold to lower values of end-tidal P CO_2. In addition, phrenic nerve responses to changes in CO_2 above the apneic threshold were augmented following microinjections of the GABA Antagonists. This augmentation resulted from larger respiratory frequency responses with slight increases in the tidal phrenic response. Microinjection of a GABA agonist into the same hypothalamic site reversed the effects of the GABA antagonist. Microinjection of the GABA agonist without a preceding antagonist injection had no effects. These results suggest that the respiratory responses to increases in P CO_2 above the apneic threshold are modulated by neurons in the posterior hypothalamus in anesthetized cats. This hypothalamic modulation involves a GABAergic mechanism.
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Posterior hypothalamic modulation of the respiratory response to CO2 in cats.
Pflugers Archiv : European journal of physiology, 1991Co-Authors: T. G. WaldropAbstract:Several studies have provided evidence that suprapontine structures are involved in modulating the respiratory response to increases in carbon dioxide. However, the actual neuroanatomical site(s) responsible for this effect has not been identified. Therefore, the purpose of the present study was to determine if the posterior hypothalamus is one rostral site involved in the modulation of the respiratory response to hypercapnia. Phrenic nerve responses to progressive step increases in end-tidal PCO2 were recorded before and after unilateral microinjection of γ-aminobutyric acid (GABA) Antagonists into the posterior hypothalamus of anesthetized cats, which were paralyzed and ventilated. Microinjection of the Antagonists reduced the apneic threshold to lower values of end-tidal PCO2. In addition, phrenic nerve responses to changes in CO2 above the apneic threshold were augmented following microinjections of the GABA Antagonists. This augmentation resulted from larger respiratory frequency responses with slight increases in the tidal phrenic response. Microinjection of a GABA agonist into the same hypothalamic site reversed the effects of the GABA antagonist. Microinjection of the GABA agonist without a preceding antagonist injection had no effects. These results suggest that the respiratory responses to increases in PCO2 above the apneic threshold are modulated by neurons in the posterior hypothalamus in anesthetized cats. This hypothalamic modulation involves a GABAergic mechanism.
Miki Akamatsu - One of the best experts on this subject based on the ideXlab platform.
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non competitive GABA Antagonists probing the mechanisms of their selectivity for insect versus mammalian receptors
Pest Management Science, 2001Co-Authors: Yoshihisa Ozoe, Miki AkamatsuAbstract:A great variety of non-competitive Antagonists of ionotropic gamma-aminobutyric acid (GABA) receptors have been reported. While they are structurally diverse, there are common features in their structures. Thus, it was hypothesized that they bind to an identical site in different or overlapping orientations, and this hypothesis was validated by three-dimensional structure-activity relationship (3D-QSAR) analysis using receptor-binding data. Meanwhile, although most Antagonists are highly toxic to both vertebrates and invertebrates, several classes of Antagonists, such as nor-diterpene lactone picrodendrins, phenyl heterocyclic compounds and disubstituted bicyclophosphorothionates, were found to exhibit selectivity for housefly versus rat GABA receptors. To probe their selectivity mechanisms, the 3D-QSAR method was applied to the three classes of Antagonists. This revealed several important differences that might be related to the selectivity of Antagonists between the structures of the non-competitive antagonist-binding sites of housefly and rat GABA receptors.
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sites of action of noncompetitive GABA Antagonists in houseflies and rats three dimensional qsar analysis
Pesticide Science, 1997Co-Authors: Miki Akamatsu, Yoshihisa Ozoe, Kazuo Mochida, Toshiie Nakamura, Tamio Ueno, Toshio Fujita, Fumio MatsumuraAbstract:Quantitative structure-activity relationships for insecticidal activity (against houseflies) and competitive activity against a specific [ 35 S]tert-butyl-bicyclophosphorothionate binding (to rat brain membranes) of some picrotoxinin-type 4-aminobutyric acid Antagonists, including γ-BHC, endosulfan, bicyclophosphates, dioxatricyclododecenes and related compounds, were examined three-dimensionally using comparative molecular field analysis (CoMFA). The Antagonists were classified into two series according to their molecular shapes: i.e. whether their structure was 'linearly' extended beyond the 'mast-head' position of the 'boat-like' skeletons (series 1) or not (series 2). The CoMFA showed that the slopes in steric and electrostatic fields around the molecule were significant for both series in governing the potency variations in insecticidal and binding activities. Hydrophobicity, a possible factor controlling transport behaviour of compounds, was significant in governing variations in insecticidal activity, but not for the case of the rat membrane binding. Assuming that there is a slight topological difference between series 1 and 2 compounds in terms of the mode of binding with the housefly receptor site, the insecticidal activity was analysable with a single equation for the combined set of compounds, but the rat membrane binding was not. The sterically and electrostatically favourable regions surrounding the molecular series indicated by CoMFA were roughly located at positions so as to interact with the binding subsites on the receptors proposed previously.
Kazuhiro Sugahara - One of the best experts on this subject based on the ideXlab platform.
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The effect of gamma-aminobutyric acid (GABA) receptor drugs on morphine-induced spastic paraparesis after a noninjurious interval of spinal cord ischemia in rats.
Anesthesia and analgesia, 2002Co-Authors: Seiya Nakamura, Manabu Kakinohana, Yutaka Taira, Hiroshi Iha, Kazuhiro SugaharaAbstract:UNLABELLED We have previously demonstrated that intrathecal morphine given after a noninjurious interval of spinal cord ischemia induced transient spastic paraparesis in a rodent model. However, the mechanism of this paraparesis is unknown. We hypothesized that morphine inhibits gamma-aminobutyric acid (GABA)ergic interneurons that control the tonus of spinal cord alpha-motoneurons and that inhibition of spinal cord interneurons may cause spastic paraparesis. In this study, we investigate interactions between morphine and GABAergic agonists or Antagonists on motor function after spinal cord ischemia and then clarified the mechanism of the spastic paraparesis induced by intrathecal morphine. Spinal cord ischemia was induced by aortic occlusion lasting 6 min. We first determined whether intrathecally administered GABA agonists (muscimol or baclofen) improve the spastic paraparesis in this model. GABA agonists did not improve the paraparesis. Next, we examined the effect of GABA Antagonists (bicuculline or 5-aminovaleric acid) and determined the interaction between morphine and GABA Antagonists. In an isobolographic analysis, the 50% effective dose decreased below the theoretical additive line, indicating a synergistic interaction between morphine and GABA Antagonists. These results indicate that the spastic paraparesis induced by intrathecal morphine may be mediated in part by GABA receptors. IMPLICATIONS The purpose of this study was to investigate interactions between morphine and GABAergic agonists or Antagonists on motor function after spinal cord ischemia and then clarify the mechanism of the spastic paraparesis induced by intrathecal morphine. The spastic paraparesis induced by intrathecal morphine may be mediated in part by GABA receptors.
