共查询到20条相似文献,搜索用时 0 毫秒
1.
Inhibitory neurotransmission is primarily governed by γ-aminobutyric acid (GABA) type A receptors (GABAARs). GABAARs are heteropentameric ligand-gated channels formed by the combination of 19 possible subunits. GABAAR subunits are subject to multiple types of regulation, impacting the localization, properties, and function of assembled receptors. GABAARs mediate both phasic (synaptic) and tonic (extrasynaptic) inhibition. While the regulatory mechanisms governing synaptic receptors have begun to be defined, little is known about the regulation of extrasynaptic receptors. We examine the contributions of GABAARs to the pathogenesis of neurodevelopmental disorders, schizophrenia, depression, epilepsy, and stroke, with particular focus on extrasynaptic GABAARs. We suggest that extrasynaptic GABAARs are attractive targets for the treatment of these disorders, and that research should be focused on delineating the mechanisms that regulate extrasynaptic GABAARs, promoting new therapeutic approaches. 相似文献
2.
3.
J E Merrill 《Journal of cellular biochemistry》1991,46(3):191-198
With the convergence of science from the fields of neurobiology and immunology, many exciting and challenging surprises have emerged regarding cytokines, neuroendocrine hormones, neuropeptides, excitatory amino acids, and their receptors. For some time neurobiologists have known that subsets of neural cells had different receptors for the same ligand. Those subsets of cells could be as different as neurons and astrocytes and as closely related as astrocytes from different lineages or anatomical areas. The neurobiological puzzle has been to determine the functional meaning of these differences. Immunologists in contrast have long understood the clear cut differences between T and B lymphocytes or T helper/inducer and T cytotoxic/suppressor cells and their response to cytokines. However, it is only very recently that they have discovered preferential use by these cells of different receptors for an identical cytokine ligand. Indeed, identical cytokines in the central nervous system and immune response may induce their pleiotropic responses by utilizing different receptors in these two systems. Immunologic paradigms may help neurobiologists predict the existence of subsets of neural cells and their function. Likewise, neurobiology may enable immunologists to predict roles for receptors in gene families as well as the existence of as yet unidentified receptors. 相似文献
4.
A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 2, pp. 269–279, March–April, 1988. 相似文献
5.
Ji Woong Choi Jerold Chun 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(1):20-32
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), two of the best-studied lysophospholipids, are known to influence diverse biological events, including organismal development as well as function and pathogenesis within multiple organ systems. These functional roles are due to a family of at least 11 G protein-coupled receptors (GPCRs), named LPA1–6 and S1P1–5, which are widely distributed throughout the body and that activate multiple effector pathways initiated by a range of heterotrimeric G proteins including Gi/o, G12/13, Gq and Gs, with actual activation dependent on receptor subtypes. In the central nervous system (CNS), a major locus for these signaling pathways, LPA and S1P have been shown to influence myriad responses in neurons and glial cell types through their cognate receptors. These receptor-mediated activities can contribute to disease pathogenesis and have therapeutic relevance to human CNS disorders as demonstrated for multiple sclerosis (MS) and possibly others that include congenital hydrocephalus, ischemic stroke, neurotrauma, neuropsychiatric disorders, developmental disorders, seizures, hearing loss, and Sandhoff disease, based upon the experimental literature. In particular, FTY720 (fingolimod, Gilenya, Novartis Pharma, AG) that becomes an analog of S1P upon phosphorylation, was approved by the FDA in 2010 as a first oral treatment for MS, validating this class of receptors as medicinal targets. This review will provide an overview and update on the biological functions of LPA and S1P signaling in the CNS, with a focus on results from studies using genetic null mutants for LPA and S1P receptors. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. 相似文献
6.
离子型谷氨酸受体分为NMDA型和非NMDA型两类,其中NMDA型受体与中枢神经系统发育关系密切。本文综述了NMDA受体的分子特性及NMDA受体五种亚单位NR1、NR2A、NR2B、NR2C和NR2D在动物出生后脑内的时空表达;NMDA受体亚单位在发育中的作用以及NMDA受体活性的胞内调节机制。 相似文献
7.
A. E. Valeev 《Neurophysiology》1986,18(2):199-207
Conclusions Recent research has raised a whole set of new and interesting points concerning the arrangement of GABA receptor sites. The most important of these is the separation of two distinct GABA receptor categories, namely bicuculline-sensitive and bicuculline-insensitive, which control the chloride and calcium conductance of the postsynaptic membrane. Information regarding the membrane and intracellular processes involved in activating GABAB receptors remains particularly limited as yet. Accordingly, findings from the literature maintain that calcium ions are not the sole transmitter of transmembrane current during activation of this category of receptor, while data from biochemical research suggests that the intracellular activity of cAMP and cGMP is changed when bicuculline-insensitive receptors are activated [15, 38]. It should be added that the physiological role played by these receptors is not yet known.The study of bicuculline-sensitive GABA receptor complexes using benzodiazepines, as well as their antagonists and reversible agonists, also offers considerable interest. Such research is particularly apposite in view of the widely discussed possibility of related endogenous-type substances existing and consequently of hitherto unknown inherent mechanisms controlling inhibitory processes within the CNS.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 2, pp. 273–282, March–April, 1986. 相似文献
8.
Degeneration and repair in central nervous system disease 总被引:1,自引:0,他引:1
Lo EH 《Nature medicine》2010,16(11):1205-1209
Divergent disease triggers in neurodegeneration may induce convergent endogenous pathways in neuronal, glial and vascular elements as the central nervous system (CNS) attempts to compensate, remodel and recover. Dissecting these multicellular mechanisms and the integrative responses in cerebral blood flow and metabolism may allow us to understand the balance between injury and repair, validate new targets and define therapeutic time windows for neurodegeneration. 相似文献
9.
Daniel P. Cardinali María I. Vacas Mónica N. Ritta Pablo V. Gejman 《Neurochemistry international》1983,5(2):185-192
Results are discussed indicating that neurotransmitters affect steroid hormone activity not only by controlling via neuroendocrine events the hypophysial-gonadal and hypophysial-adrenal axes, but also by modulating cell responsiveness to steroids in target cells. Hyper- or hypoactivity of pineal nerves result in enhancement or impairment of estradiol and testosterone effects on pineal metabolism in vivo and in vitro. Pineal cytoplasmic and nuclear estrogen and androgen receptors are modulated by norepinephrine released from nerve endings at the pinealocyte level. Neural activity affects the cycle of depletion-replenishment of pineal estrogen receptors following estradiol administration. Another site of modulation of steroid effects on the pinealocytes is the intracellular metabolism of testosterone and progesterone; nerve activity has a positive effect on testosterone aromatization and a negative effect on testosterone and progesterone 5α-reduction. NE activity on the pineal cells is mediated via β-adrenoceptors and cAMP. In the central nervous system information on the neurotransmitter modulation of steroid hormone action includes the following observations: (a) hypothalamic deafferentation depresses estrogen receptor levels in rat medial basal hypothalamus; (b) changes in noradrenergic transmission affect, via α-adrenoceptors, the estradiol-induced increase of cytosol progestin receptor concentration in guinea pig hypothalamus; (c) cAMP increases testosterone aromatization in cultured neurons from turtle brain; (d) electrical stimulation of dorsal hippocampus augments, and reserpine or 6-hydroxydopamine treatment decrease, corticoid binding in cat hypothalamus. In the adenohypophysis changes in dopaminergic input after median eminence lesions or bromocriptine treatment of rats result in opposite modifications of pituitary estrogen receptor levels. Therefore all these observations support the view that neurotransmitters can modulate the attachment of steroid hormones to their receptors in target cells. 相似文献
10.
11.
1. Multiple distinct affinity states or sites of substance P (SP) receptors exist in freshly-prepared rat brain membranes. 2. Substance P receptors may couple with islet-activating protein (pertussis toxin) sensitive GTP-binding protein(s). 3. Substance P receptors may be regulated Mg2+ and Na+ in an opposite manner. 4. Some important factor(s), in addition to GTP-binding protein, appear to be involved in SP binding activity. 5. An apparent molecular weight of the SP binding site is approximately 46,000 Da. 相似文献
12.
Adenosine receptors in the central nervous system: relationship to the central actions of methylxanthines 总被引:45,自引:0,他引:45
Adenosine has a significant role in many functions of the central nervous system. Behaviorally, adenosine and adenosine analogs have marked depressant effects. Electrophysiologically, adenosine reduces spontaneous neuronal activity and inhibits transsynaptic potentials interaction with extracellular receptors. Biochemically, adenosine inhibits adenylate cyclase a “high” affinity receptor, and activates adenylate cyclase a “low” affinity receptor. These receptors, called “A1” and “A2” respectively, show differing profiles for activation by adenosine analogs. Radioactive N6-cyclohexyladenosine binds selectively to the “high” affinity receptor. One major class of antagonists is known at adenosine receptors: the alkylxanthines, including caffeine and theophylline. Radioactive 1,3-diethyl-8-phenylxanthine, a particularly potent antagonist, appears to bind to both low and high affinity adenosine receptors. Behavioral, electrophysiological, and biochemical effects of alkylxanthines are consistent with the hypothesis that the central stimulatory actions of caffeine and theophylline are due in large part to antagonism of central adenosine receptors. 相似文献
13.
Fibroblast growth factors (FGFs) and their receptors constitute an elaborate signaling system that participates in many developmental and repair processes of virtually all mammalian tissues. Among the 23 FGF members, ten have been identified in the brain. Four FGF receptors (FGFRs), receptor tyrosine kinases, are known so far. Ligand binding of these receptors greatly depends on the presence of heparan sulfate proteoglycans, which act as low affinity FGFRs. Ligand binding specificity of FGFRs depends on the third extracellular Ig-like domain, which is subject to alternative splicing. Activation of FGFRs triggers several intracellular signaling cascades. These include phosphorylation of src and PLC leading finally to activation of PKC, as well as activation of Crk and Shc. SNT/FRS2 serves as an alternative link of FGFRs to the activation of PKC and, in addition, activates the Ras signaling cascade. In the CNS, FGFs are widely expressed; FGF-2 is predominantly synthesized by astrocytes, whereas other FGF family members, e.g., FGF-5, FGF-8, and FGF-9, are primarily synthesized by neurons. During CNS development FGFs play important roles in neurogenesis, axon growth, and differentiation. In addition, FGFs are major determinants of neuronal survival both during development and during adulthood. Adult neurogenesis depends greatly on FGF-2. Finally, FGF-1 and FGF-2 seem to be involved in the regulation of synaptic plasticity and processes attributed to learning and memory. 相似文献
14.
中枢神经系统疾病因其发病机制复杂而难以找到药物作用的有效靶点。甘丙肽(galanin, GAL)因其广泛的中枢神经系统分布并与多种神经系统疾病密切相关而进入人们的视线。现已证明,GAL与三种G蛋白偶联受体(GALR1-3)结合后,通过抑制cAMP/PKA(GALR1、GALR3)和激活磷脂酶C(GALR2)等信号通路调节众多生理和病理过程。本文概述了近年来GAL及其受体在中枢神经系统疾病中的作用的研究进展,旨在为理解这些疾病的发病机制以及靶向药物的研发提供新的指导。 相似文献
15.
16.
The 5-HT3 receptor is a ligand-gated ion channel activated by serotonin (5-HT). Although originally identified in the peripheral nervous system, the 5-HT3 receptor is also ubiquitously expressed in the central nervous system. Sites of expression include several brain stem nuclei and higher cortical areas such as the amygdala, hippocampus, and cortex. On the subcellular level, both presynaptic and postsynaptic 5-HT3 receptors can be found. Presynaptic 5-HT3 receptors are involved in mediating or modulating neurotransmitter release. Postsynaptic 5-HT3 receptors are preferentially expressed on interneurons. In view of this specific expression pattern and of the well-established role of 5-HT as a neurotransmitter shaping development, we speculate that 5-HT3 receptors play a role in the formation and function of cortical circuits. 相似文献
17.
18.
19.