Abstract:
:Outer (OHC) and inner (IHC) hair cells in the organ of Corti of the mammalian cochlea process sound. OHC and their efferent synapse are part of a feedback system assumed to control and modulate information carried by afferent neurons passing from IHC to the brain. Underlying mechanisms are not well understood. This paper discusses recent progress. In vivo and in vitro information is presented on structure, pharmacology, function and localization of the pre- and postsynaptic acetylcholine receptors (AChRs) at the efferent synapse. Recent data are given on a presynaptic M3 AChR subtype, probably an autoreceptor involved in transmitter release. Data from our lab on specific binding of [3H]3-quinuclidinyl benzilate ([3H]3-QNB) to non-enzymatically isolated guinea pig OHC reveal a KD several 100 x higher than that for any known muscarinic receptor subtype, including the above-mentioned presynaptic muscarinic AChR of the OHC efferent synapse. The extremely high concentrations of [3H]3-QNB needed for any binding at all to OHC thus rule out presynaptic membrane impurities as the cause of such binding, and also the presence of a typical mAChR subtype on OHC. The number of [3H]3-QNB binding sites (approximately 10(6)/OHC) we found on OHC was 1/10th of that we found for binding of nicotinic ligands to OHC, further making it questionable that an ACh-binding site on OHC binds [3H]3-QNB. Observations may instead point to the possibility of another binding site, e.g. an (allosteric) site involved with the as yet not understood 'weak' muscarinic properties of the OHC AChR. Further new data on the OHC AChR confirm reversible alpha-bungarotoxin, nicotine and d-tubocurarine binding. [3H]alpha-Bungarotoxin and [3H]-nicotine binding sites are estimated at approximately 6.10(7) sites/OHC. Strychnine, a glycine receptor blocker suggested to interfere with cholinergic sites of the efferent OHC synapse, was found to bind to OHC (cold strychnine for unspecific binding). This binding, not seen in the presence of high [glycine], increased in the presence of depolarizing [K+], while ACh (100 microM) had no significant effect. Results suggest strychnine binding to the outside of OHC, but also sites accessible only after cell depolarization, possibly to the hyperpolarizing Ca2(+)-dependent K+ channel. Recent molecular cloning of the OHC AChR indicates a novel alpha-subunit. An often observed ACh-activated Ca(2+)-influx close to zero into OHC leaves an unanswered question. OHC also carry P2-purinergic receptors (P2Rs), a more rapid ionotropic P2zR-like subtype and a quantitatively dominating slow metabotropic P2yR subtype coupled to a G protein-phospholipase C cascade and not desensitized. Both contribute to increased cytoplasmic [Ca2+], from respectively external and internal sources. Whether or not such receptors are part of efferent synaptic activity is unknown; their localization on the OHC plasma membrane is so far only indirect and synaptic vesicles of the efferent nerve endings have not yet been analyzed for their ATP content. Localization, function and interaction of [Ca2+] increases triggered by, respectively, ATP and ACh are currently studied in this laboratory.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Heilbronn E,Järlebark L,Lawoko Gdoi
10.1016/0197-0186(95)00011-vsubject
Has Abstractpub_date
1995-10-01 00:00:00pages
301-11issue
4-5eissn
0197-0186issn
1872-9754journal_volume
27pub_type
杂志文章,评审abstract::Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifest...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2017.07.008
更新日期:2018-07-01 00:00:00
abstract::Mecamylamine is a well-described non specific antagonist of nicotinic acetylcholine receptors (nAChRs), used in therapy and in psychopharmacological studies. [(11)C]-Mecamylamine was prepared and evaluated as a putative radioligand for positron emission tomography to study nicotinic acetylcholine receptors. The radios...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2004.12.003
更新日期:2005-05-01 00:00:00
abstract::The effects of the GABA agonist, muscimol on [(3)H]flunitrazepam binding were examined in cerebellum and hippocampus regions proposed to contain different populations of benzodiazepine binding site subtypes. Quantitative analysis was made of the contribution of different components of [(3)H]flunitrazepam binding by ut...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(84)90082-2
更新日期:1984-01-01 00:00:00
abstract::Activation of astrocytes occurs during many forms of CNS injury, but its importance for neuronal survival is poorly understood. When hippocampal cultures of neurons and astrocytes were treated from day 2-4 in vitro (DIV 2-4) with 1 microM cytosine arabinofuranoside (AraC), we observed a stellation of astrocytes, an in...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(02)00164-x
更新日期:2003-06-01 00:00:00
abstract::Phosphine-borane complexes are novel cell-permeable drugs that protect neurons from axonal injury in vitro and in vivo. These drugs activate the extracellular signal-regulated kinases 1/2 (ERK1/2) cell survival pathway and are therefore neuroprotective, but do not scavenge superoxide. In order to understand the intera...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2016.05.014
更新日期:2016-10-01 00:00:00
abstract::Striatal quinolinic acid lesions have been used as a model for the pathology seen in Huntington's disease. Seven days following a unilateral injection of 100 nmol of quinolinic acid into the rat caudate-putamen (striatum), a large increase in the binding of [3H]WIN 35,428 to the lesioned caudate-putamen was seen when ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(92)90091-5
更新日期:1992-12-01 00:00:00
abstract::It is well established that histaminergic neurons in the posterior hypothalamus make connections with whole brain areas and regulate several functions. Recent evidence indicates that histaminergic neurons are heterogeneous cell group and organized into distinct circuits. However, functional circuits of histaminergic n...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2012.05.022
更新日期:2012-11-01 00:00:00
abstract::This report describes the effects of endothelins (ET-1 and ET-3) on ion transport systems expressed on cultured rat brain capillary endothelial cells (RBEC) and includes investigation of pharmacological properties of ET receptors, their reactivity and induction of signal transduction pathways. ET-1 stimulated IP3 form...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(97)00018-1
更新日期:1997-10-01 00:00:00
abstract::While studies with [(3)H]D-aspartate ([(3)H]d-Asp) illustrate specific interactions with excitatory amino acid transporters (EAATs), new insights into the pharmacological characteristics and localization of specific EAAT subtypes depend upon the availability of novel ligands. One such ligand is [(3)H]-(2S,4R)-4-methyl...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2007.05.011
更新日期:2007-12-01 00:00:00
abstract::25INBOMe ("25-I", "N-Bomb"), one of new psychoactive substances (NPSs), is being abused for recreational purpose. However, the liability for abuse or dependence has not been systematically studied yet. The objective of the present study was to evaluate rewarding and reinforcing effects of 25INBOMe using conditioned pl...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2019.02.007
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abstract::Vinpocetine (ethyl apovincaminate), a synthetic derivative of the Vinca minor alkaloid vincamine, is widely used for the treatment of cerebrovascular-related diseases. One of the proposed mechanisms underlying its action is to protect against the cytotoxic effects of glutamate overexposure. Glutamate excitotoxicity le...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2008.08.003
更新日期:2008-12-01 00:00:00
abstract::D1 and D2 receptors are key mediators of dopaminergic signaling in the brain, and since the manifestations of pathologies related to dopamine are different in female and male patients, it is important to analyze if there are sex-related differences in dopaminergic markers. To contribute to the knowledge in this regard...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2016.09.001
更新日期:2016-11-01 00:00:00
abstract::Long-term (12 h) incubation of NCB-20 neuroblastoma x Chinese hamster brain cell hybrid cells with phorbol dibutylate caused a decrease in the enzyme activity of protein kinase C (PKC). Under these conditions, the formation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] and the mobilization of intracellular Ca(2+) t...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(91)90175-d
更新日期:1991-01-01 00:00:00
abstract::To identify whether the process of apoptosis bears a topographic relationship to selected aspects of Alzheimer's disease (AD) pathology, we used an in situ nick translation method (TUNEL) to map DNA fragmentation in hippocampal sections immunostained for abnormally phosphorylated tau, which exists in the neurofibrilla...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(96)00158-1
更新日期:1997-08-01 00:00:00
abstract::Many pharmacological and toxicological studies of centrally acting drugs are undertaken in animals at doses expressed in mg.kg-1, and the results extrapolated to the clinical dose in man. Safety margins based on such no or lowest effect levels may have little relevance since they do not take into account differences i...
journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/0197-0186(94)00104-3
更新日期:1995-02-01 00:00:00
abstract::Chronic pain states and epilepsies are common therapeutic targets of voltage-gated sodium channel blockers. Inhibition of sodium channels results in central muscle relaxant activity as well. Selective serotonin reuptake inhibitors are also applied in the treatment of pain syndromes. Here, we investigate the pharmacody...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2006.12.008
更新日期:2007-03-01 00:00:00
abstract::The presence of nicotinic and muscarinic receptors suggests the occurrence of cholinergic neurotransmission in white matter; however no quantitative information exists on acetylcholine formation and breakdown in white matter. We compared white structures of pig brain (fimbria, corpus callosum, pyramidal tracts, and oc...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2008.06.008
更新日期:2008-12-01 00:00:00
abstract::The influence of alpha2-autoreceptors on the facilitation of [3H]-noradrenaline release mediated by angiotensin II was studied in prostatic portions of rat vas deferens preincubated with [3H]-noradrenaline. Angiotensin II enhanced tritium overflow evoked by trains of 100 pulses at 8 Hz, an effect that was attenuated b...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2006.07.002
更新日期:2006-12-01 00:00:00
abstract::Cholesterol, a molecule critical for cellular function, is found in particular high concentration in the brain and has been implicated to synaptic plasticity and neuronal regeneration. This study was undertaken to investigate the mechanism by which cholesterol shortage modulates glutamate (Glu)-induced excitotoxicity ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(03)00003-2
更新日期:2003-08-01 00:00:00
abstract::The protein kinase C (PKC) family of serine/threonine kinase isoenzymes are universally expressed in vertebrate tissues where they control vital cellular functioning. PKC comprises twelve currently identified mammalian isoenzymes, described in three distinct groups according to their need for different effector stimul...
journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/s0197-0186(96)00049-6
更新日期:1997-02-01 00:00:00
abstract::We have previously demonstrated that acute hyperhomocysteinemia induces oxidative stress in rat brain. In the present study, we initially investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative damage, namely total radical-trapping antioxidant potential and activities of antioxidant enz...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2008.08.011
更新日期:2009-01-01 00:00:00
abstract::It has been shown recently that the N-terminal domain of the dopamine transporter (DAT) plays a role in several transporter functions. Here we provide evidence for a possible cellular mechanism of how the N-terminus of dopamine transporter might be removed in vivo. We isolated a recombinant N-terminal protein region o...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2008.04.001
更新日期:2008-06-01 00:00:00
abstract::Glutamate is an excitotoxin responsible for causing neuronal damage associated with mitochondria dysfunction. We have analyzed the relationship between the mitochondrial respiratory rate, the membrane potential (delta psi) and the activity of mitochondrial complexes in retinal cells in culture, used as neuronal models...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(99)00107-2
更新日期:2000-02-01 00:00:00
abstract::Neosurugatoxin, a neurotoxin isolated from the Japanese ivory mollusc (Babylonia japonica ) is a nicotinic antagonist with a specificity towards ganglionic nicotinic receptors. At low concentration (5 x 10(?8) M) neosurugatoxin inhibited the release of [(3)H]dopamine evoked by 1,1-dimethyl-4-phenylpiperazinium (DMPP) ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(85)90131-7
更新日期:1985-01-01 00:00:00
abstract::Resistance to inhibitors of cholinesterase (RIC) -3 promotes the maturation (folding and assembly) of neuronal nicotinic acetylcholine receptors (nAChRs) as a molecular chaperone. The modulation effects of RIC-3 on homomeric α7 nAChRs are always positive, but its effects on heteromeric subtypes are inconsistent among ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2017.10.007
更新日期:2018-05-01 00:00:00
abstract::Interferon beta-1b (IFN beta-1b) (Betaseron) has been recently shown to alter the course of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) where migration of activated lymphocytes across the blood-brain barrier (BBB) is a critical step in the pathogenesis of this dis...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(96)00081-2
更新日期:1997-04-01 00:00:00
abstract::TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of ubiquitinated inclusions in motor neurons of sporadic amyotrophic lateral sclerosis (ALS). TDP-43 is ubiquitously expressed and the majority of TDP-43 is normally localized to the nucleus. In motor neurons of patients with ALS, TDP-43 is not locali...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2018.12.009
更新日期:2019-03-01 00:00:00
abstract::The alternative routes of cleavage of the amyloid precursor protein (APP) result in the generation and secretion of both soluble APP and beta-amyloid, the latter being the main component of the amyloid deposits in the brains of individuals with Alzheimer's disease (AD). This study examined the question of whether acet...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(00)00091-7
更新日期:2001-03-01 00:00:00
abstract::Electroacupuncture has been shown to induce a preconditioning effect in the brain. The mechanisms for this protection are not fully elucidated. We hypothesize that this protection is mediated by excitatory amino acid transporters (EAATs) that have been shown to be neuroprotective. To test this hypothesis, two-month ol...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2013.06.017
更新日期:2013-10-01 00:00:00
abstract::Ex vivo(1)H NMR spectroscopy was used to measure changes in the concentrations of cerebral metabolites in the prefrontal cortex (PFC) and hippocampus of rats subjected to repeated morphine treatment known to cause tolerance/dependence. The results show that repeated morphine exposure induces significant changes in the...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2006.09.012
更新日期:2007-01-01 00:00:00