Endothelin‐1 increases the levels of mRNA and protein of muscarinic acetylcholine receptors and c‐<i>fos</i> mRNA in cerebellar granule cells

Fukamauchi, Fumihiko; Chuang, De‐Maw

doi:10.1016/0014-5793(94)00611-3

Cited by 11 publications

(4 citation statements)

References 23 publications

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“…There is no evidence to explain the events that occur after NMDA-induced Ca+ + increase and the activation of PAC and AAT, but it could be possible that NMDA or K + could induce an enhancement in the translation rate and/or the stabilization of the mRNA for these enzymes, as it has been shown for other proteins in the same preparation (Fukamuchi and Chuang, 1994). Both the stabilization and the increase in the synthesis rate of mRNA could be controlled by molecules that modulate the genic expression.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the activation of glutaminase induced by N-methyl-D-aspartate and potassium in cerebellar granule cells

Alavez¹,

Gutiérrez‐Kobeh²,

Morán³

1996

J. Neurosci. Res.

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Chronic stimulation of cerebellar granule cells with N‐methyl‐D‐aspartate (NMDA) or KCl induces a specific activation of the enzymes directly involved in glutamate neurotransmitter synthesis. Phosphate‐activated glutaminase (PAG) activity is enhanced in cultured granule neurons incubated with 150 μM NMDA or 25 mM KCl. Other enzymes are not affected by this treatment like lactate dehydrogenase (LDH) and glutamate dehydrogenase (GLDH), which is also a mitochondrial enzyme but not directly involved in neurotransmitter synthesis. This effect is dependent on protein synthesis and is induced after 12 hr of NMDA or KCl stimulation. Kinetics of PAG activity showed that Km values were unaffected, in contrast to Vmax values that were increased approximately 70% and 215% over control by NMDA and KCl treatment, respectively. For GLDH, we found two isoforms that were affected differentially by the experimental conditions. Western blot analysis clearly evidenced an increase of approximately 120–180% in the amount of PAG in NMDA‐ and KCl‐treated cells, whereas GLDH was not significantly modified. These results demonstrate that the NMDA‐ and KCl‐induced activation of PAG are not due to the modification of the preexisting enzyme, but to an increase in the synthesis of this enzyme. This suggests that NMDA receptor stimulation during critical periods of the cerebellar granule cell development leads to the activation of gene expression involved in the process of cell differentiation. © 1996 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Characterization of the activation of glutaminase induced by N-methyl-D-aspartate and potassium in cerebellar granule cells

Alavez¹,

Gutiérrez‐Kobeh²,

Morán³

1996

J. Neurosci. Res.

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“…In mouse embryo astrocytes that express predominantly ET B receptors, ET-1 induces phospholipase D activation [29], glutamate release [143], stimulation of c-fos and nerve growth factor expression [93], glucose uptake [165] as well as DNA synthesis [24]. At the level of gene expression, ET-1 increases the expression of c-fos in neurons and glia in organotypic culture of rat cerebellum [163] and the expression of m2 and m3 muscarinic acetylcholine receptors in cerebellar granule cells, this latter effect being likely mediated by increased c-fos expression [40]. The stimulation of ET B receptors may elicit other responses in primary rat astrocytes.…”

Section: Signal Transduction Pathways Activated By Endothelins In Thementioning

confidence: 97%

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Schinelli¹

2006

CMC

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The endothelin system, consisting of three peptides, two peptidases and two G-protein coupled receptors, is widely expressed in the brain cell types and brain-derived tumor cell lines. The stimulation of endothelin receptors elicits a variety of short- and long-term changes at cellular level but the effects of the pharmacological modulation of the endothelin system in brain physiology and pathophysiology are, at the present time, poorly understood. Altered expression of endothelins (ETs) in reactive astrocytes has been observed in many pathological conditions of the human brain, such as infarcts, lacunae, traumatic conditions, Alzheimer's disease and inflammatory diseases of the brain. In addition, recent studies have shown that endothelin antagonists might inhibit growth and induce cell death in human melanoma cells in vitro and in vivo, and have emphasized a possible role of endothelin peptides as autocrine or paracrine factor in the proliferation and dissemination of tumor cell lines. Given the fact that brain cell and a variety of brain tumor cell lines express functional endothelin receptors, further studies are warranted to demonstrate a possible therapeutic role of endothelin agonists and antagonist in the pharmacological treatment of brain-related diseases and brain tumors.

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“…While ETs have been shown previously to induce c-fos transcription in cultured neurones, 24,25 this is the first report showing that c-fos is induced in the CNS after in vivo administration of ETs to the striatum. We suggest that in the striatum, ETs modulate the activity of glutamatergic neurones, and that a glutamate-mediated activation of NMDA receptors causes the seizures seen after ET-1.…”

Section: Resultsmentioning

confidence: 81%

Cortical induction of c-fos by intrastriatal endothelin-1 is mediated via NMDA receptors

Ds²,

Kl³

et al. 1996

NeuroReport

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Intracerebral administration of endothelins (ETs) to rats induces a distinct and unusual behavioural syndrome which includes barrel-rolling and other seizures. 1,2 The mechanisms by which ETs produce these behaviours are not known, although it is generally considered that the action of ET in the CNS is mediated via a vasoconstrictor action on the cerebral vasculature. 3 ET receptors are not restricted to the vasculature, but are widely expressed throughout the brain. 4,5 Further, while the action of ETs on blood vessels is undisputed, there is growing evidence for a direct action of ETs on neurones, most of which comes from in vitro studies where neurones and glia are grown in the absence of vascular elements. [6][7][8] We tried to determine whether ETs act directly on neurones in vivo, using the expression of the immediate early gene c-fos as a marker of neuronal activation. 9 Transcription of c-fos is known to be induced in neuronal pathways in response to intrastriatal injection of excitotoxins, with different agonists inducing patterns of Fos expression different from each other. 9-12 and also distinct from those induced by ischaemia. 10,13 The pattern of c-fos expression induced by intrastriatal injection of ET-1 was examined, and compared with that reported after excitotoxin administration and forebrain ischaemia. The possible involvement in ET action of Nmethyl-D-aspartate (NMDA) receptors and of nitric oxide (NO) synthesis were also examined. Materials and MethodsIntrastriatal stereotaxic injection of ET-1: Adult male Sprague-Dawley rats were anaesthetized with halothane in nitrous oxide/oxygen. Halothane was used to induce anaesthesia, as recovery is rapid, and observation of the behaviour of the rats within the first 30 min after treatment was required. Twelve rats were given stereotaxic intrastriatal injections of ET-1 (0.1 nmol in 0.9% saline, injected in a volume of 1 l over a period of 2 min 3 ). Three additional rats were given control injections of saline alone. The coordinates used for all injections were 1 mm anterior and 2.5 mm lateral from bregma and 5 mm ventral from the dura mater, with the incisor bar at the interaural line. Pre-treatment with MK-801 (dizocilpine) or L-NNA (N -nitro-L-arginine):Three rats were treated with the NMDA receptor antagonist MK-801 (5 mg kg -1 , i.p.) 1 h before injection of ET-1. A further three rats were treated with the NOS inhibitor L-NNA (3 mg kg -1 , i.p.) 1 h before ET-1 injection. The behaviour of all rats was observed from the time of ET injection until sacrifice. Nine rats (three from ET-1 alone group, two from MK-801 group, two from L-NNA group and two from control group) were sacrificed 30 min after injection, and the brains were processed for in situ hybridization. The remaining five rats were sacrificed 1 h after the injection, by which time seizure activity had ceased. Seizures were scored using a modification of the Racine classification. 14 Neuropharmacology and Neurotoxicology 1 11 11 11 11 11 1p © Rapid Science Publishers Vol 8 No 1 20 December ...

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Endothelin‐1 increases the levels of mRNA and protein of muscarinic acetylcholine receptors and c‐fos mRNA in cerebellar granule cells

Cited by 11 publications

References 23 publications

Characterization of the activation of glutaminase induced by N-methyl-D-aspartate and potassium in cerebellar granule cells

Characterization of the activation of glutaminase induced by N-methyl-D-aspartate and potassium in cerebellar granule cells

Pharmacology and Physiopathology of the Brain Endothelin System: An Overview

Cortical induction of c-fos by intrastriatal endothelin-1 is mediated via NMDA receptors

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