Abstract:
:Positron-emitting beta-adrenoceptor ligands for the CNS could allow determination of changes in beta-adrenoceptor availability after treatment of patients with norepinephrine reuptake inhibitors or tricyclic antidepressants, and differential diagnosis between multiple sclerosis and other brain disorders in an early stage of the disease. No ligands suitable for this purpose are available for human use. In order to prepare a tracer for human studies, we labeled the biologically active enantiomer of the beta-blocker exaprolol with (11)C. Exaprolol has the appropriate lipophilicity (log P + 1.6) for entry of the CNS and is claimed to be a very potent beta-adrenoceptor antagonist. (S)-Desisopropyl-exaprolol was synthesized by reaction of 2-hexylphenol with (S)-glycidyl-nosylate followed by ring opening using ammonia gas. The desisopropyl precursor was reacted with (11)C-acetone in methanol to produce (S)-[(11)C]-exaprolol. Radiochemical purification was performed with RP-HPLC and was followed by Sep-Pak formulation. The labeled product was i.v. injected into male Wistar rats. Brain images were acquired using a microPET Focus 220 and the biodistribution of (11)C was assessed. The radiochemical yield of (S)-[(11)C]-exaprolol was 7% with a total synthesis time of 30 min. Specific activities were >10 GBq/micromol. Brain uptake of the tracer reached a maximum after 15 min. Standardized uptake values were moderate (0.5-0.9) but sufficient for imaging. However, beta-blockade (propranolol, 2.5mg/kg body weight) did not lower tracer uptake in any CNS region and washout from the brain was not accelerated when propranolol was administered 40 min after injection of (S)-[(11)C]-exaprolol. Tracer binding in lung, spleen and erythrocytes was lowered after beta-blockade, but the myocardial uptake of radioactivity was not affected. These data indicate that (S)-[(11)C]-exaprolol is not a suitable beta-adrenoceptor ligand for PET, probably because the in vivo affinity of exaprolol to beta-adrenoceptors is in the nM rather than the sub-nM range. The observed inhibition of tracer uptake in lung, spleen and erythrocytes seems due to an interaction of propranolol with amine transporters rather than beta-adrenoceptors.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
van Waarde A,Doorduin J,de Jong JR,Dierckx RA,Elsinga PHdoi
10.1016/j.neuint.2007.09.009subject
Has Abstractpub_date
2008-03-01 00:00:00pages
729-33issue
4-5eissn
0197-0186issn
1872-9754pii
S0197-0186(07)00254-9journal_volume
52pub_type
杂志文章abstract::Neuropathic pain is a type of chronic pain caused by nervous system damage and dysfunction. The pathogenesis of chronic pain is complicated, and there are no effective therapies for neuropathic pain. Studies show that the P2X4 receptor expressed in the satellite glial cells (SGCs) of dorsal root ganglia (DRG) is relat...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2017.02.004
更新日期:2017-09-01 00:00:00
abstract::In order to elucidate the effects of MPTP on enkephalinergic neurons, dopamine (DA), norepinephrine (NE), proenkephalin (PE) mRNA and met-enkephalin (ME) were measured in striatum, olfactory tubercle, and prefrontal cortex of C57/B16 mice 1 day-2 weeks following treatment with 96 mg/kg MPTP HCl (24 mg/kg i.p., twice/d...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(93)90010-3
更新日期:1993-02-01 00:00:00
abstract::Even though the inducing effect of electromagnetic fields (EMF) on the neural differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) is a distinctive, the underlying mechanism of differentiation remains unclear. To find out the signaling pathways involved in the neural differentiation of BM-MSCs by EMF...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2013.02.002
更新日期:2013-03-01 00:00:00
abstract::Age is the leading risk factor for many of the most prevalent and devastating diseases including neurodegenerative diseases. A number of herbal medicines have been used for centuries to ameliorate the deleterious effects of ageing-related diseases and increase longevity. Oxidative stress is believed to play a role in ...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2012.08.018
更新日期:2013-04-01 00:00:00
abstract::Recent studies have suggested that neurosteroids such as pregnenolone, progesterone (PG) and their derivatives, have a role in activating autophagy in addition to diverse other functions. In our previous studies, we demonstrated that cellular free Zn(2+) is involved in oxidative stress-induced autophagy and autophagic...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2011.11.015
更新日期:2012-01-01 00:00:00
abstract::The effects of hypoxia on the metabolism of the central nervous system were investigated in rats submitted to a low oxygen atmosphere (8% O(2); 92% N(2)). [1-(13)C]glucose and [2-(13)C]acetate were used as substrates, this latter being preferentially metabolized by glial cells. After 1-h substrate infusion, the incorp...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/s0197-0186(00)00106-6
更新日期:2001-04-01 00:00:00
abstract::The effect of subcutaneous injections of saline (0.9% NaCl, 10-40 ?l/g b. wt) to 5- and 20-day old rats on the concentrations of tyrosine (Tyr) and tryptophan (Trp) in the serum and the brain and on the levels of biogenic amines and their metabolites in the developing brain at 6 h p.i. is described. At day 5 the conce...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(85)90071-3
更新日期:1985-01-01 00:00:00
abstract::Previously, we revealed that the state of the actin cytoskeleton affects the uptake activity of the serotonin transporter (SERT). Recently, it was reported that the C-terminus of SERT interacts with MacMARCKS, a substrate of PKC that can bind to the actin cytoskeleton. To elucidate the importance of the C-terminal reg...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2004.08.008
更新日期:2005-01-01 00:00:00
abstract::This study aimed to elucidate locomotor activity changes in 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) and investigate the possible beneficial effects of melatonin on altered levels of locomotor activity, cyclooxygenase (COX), prostaglandin E2 (PGE2), nuclear factor kappa-B (NF-κB), nitrate/nitrite an...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2014.09.005
更新日期:2014-12-01 00:00:00
abstract::A simple, rapid and sensitive method for the detection of acetylcholine and choline in tissue extracts is reported. Acetylcholine and choline are first separated by HPLC then react in a mini-column with acetylcholinesterase and choline oxidase immobilized on Sepharose. The resulting H(2)O(2) produced by choline oxidas...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(86)90041-0
更新日期:1986-01-01 00:00:00
abstract::Streptozotocin (STZ) is a glucosamine-nitrosourea commonly used to induce long-lasting models of diabetes mellitus and Alzheimer's disease. Direct toxicity of STZ on the pancreas and kidneys has been well characterized, but the acute effect of this compound on brain tissue has received less attention. Herein, we inves...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2019.04.013
更新日期:2019-09-01 00:00:00
abstract::The parenchyma of the anterior pituitary gland is constituted of distinct specialized glandular cell types, some of them being able to secrete two, or more, genetically related hormones. The synthesis and the release of each hormone is a discontinuous process controlled by a variety of chemical signals of hypothalamic...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(85)90146-9
更新日期:1985-01-01 00:00:00
abstract::Phosphodiesterase 7B (PDE7B) inhibition has been considered as a therapeutic target for the treatment of several neurological disorders. Currently, there are no radio-labeled tracers available to determine receptor occupancy (RO) of this target. Developing such a tracer could greatly facilitate the identification of v...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2020.104735
更新日期:2020-07-01 00:00:00
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2009.10.001
更新日期:2010-01-01 00:00:00
abstract::Free radicals have been implicated in the pathogenesis of vasogenic brain edema caused by ischemic or traumatic injury. It has been reported that in transgenic mice overexpressing the human CuZn-superoxide dismutase, brain edema is decreased in many cerebral disorders. To investigate the effects of free radicals on th...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(95)00120-4
更新日期:1996-08-01 00:00:00
abstract::Zinc transporter 3 (ZNT3) has been shown to transport zinc ions from the cytosol into presynaptic vesicles in the mammalian brain. Several studies have stated that the zinc ion containing synaptic vesicles of zinc-enriched neurons (ZEN) are loaded with ZNT3 proteins in their membranes. This fact makes it possible to t...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2008.02.008
更新日期:2008-06-01 00:00:00
abstract::In this study we determined the changes in the intracellular free Ca2+ concentration, associated with the inhibitory modulation of the exocytotic release of GABA by GABAB receptor activation in rat cerebrocortical synaptosomes. We observed that SK&F 97541 and (-)baclofen both act as agonists of the presynaptic GABAB r...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(95)00021-y
更新日期:1995-10-01 00:00:00
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journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(80)90085-6
更新日期:1980-01-01 00:00:00
abstract::The N-methyl-D-aspartate (NMDA) receptor is a subtype of ionotropic glutamate receptor that is involved in synaptic mechanisms of learning and memory, and mediates excitotoxic neuronal injury. In this study, we tested the hypothesis that NMDA receptor subunit gene expression is altered in cortex and hippocampus of OKA...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2014.06.012
更新日期:2014-10-01 00:00:00
abstract::Dysregulation of blood-brain barrier (BBB) transport exacerbates brain damage in acute ischemic stroke. Here, we aimed to investigate the mechanism of this BBB transport dysregulation by studying the localization and function of pannexin (Px) and connexin (Cx) hemichannels in blood-brain barrier endothelial cells of r...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2019.104600
更新日期:2020-01-01 00:00:00
abstract::Esters of dimethylcarbamic acid are known to be poor substrates of acetylcholinesterase. They carbamylate the active catalytic site of the enzyme and the subsequent decarbamylation is a slow but measurable process. Similarly, acetylcholinesterase can be phosphonylated, and the dephosphonylation is extremely slow. Rapi...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(81)90061-9
更新日期:1981-01-01 00:00:00
abstract::The effects of subcutaneous (s.c.) oxytocin treatment have been investigated on various parameters of dopaminergic neurotransmission in basal forebrain structures (nucleus olfactorius posterior + nucleus accumbens + septum) of the mouse. Acute oxytocin treatment failed to influence dopamine utilization in the basal fo...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(86)90138-5
更新日期:1986-01-01 00:00:00
abstract::Tau isoforms constitute a family of microtubule-associated proteins that are mainly expressed in neurons of the central nervous system. They promote the assembly of tubulin monomers into microtubules and modulate their stability, thus playing a key structural role in the distal portion of axons. In Alzheimer's disease...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2011.02.010
更新日期:2011-05-01 00:00:00
abstract::Thromboxane A2(TxA2) is a potent vasoconstrictor associated with cerebrovascular disease and is thought to be synthesized within tissues of the brain. In order to determine the cellular sources of TxA2 in the central nervous system (CNS), we measured the release of the stable metabolite TxB2 in cultures of mixed or hi...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(95)00140-9
更新日期:1996-07-01 00:00:00
abstract::5,7-Dihydroxytryptamine (5,7-DHT) is a selective serotonergic neurotoxin by virtue of its selective uptake into 5-hydroxytryptamine neurons and its ability to undergo autoxidation. The mechanism by which 5,7-DHT induces neurodegenerative effects remains enigmatic. The mechanism of autoxidation of 5,7-DHT, which has be...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(88)90165-9
更新日期:1988-01-01 00:00:00
abstract::The effect of GM(1) administration upon the time course of the postlesion changes of [(3)H]5hydroxytryptamine uptake in the partially denervated rat hippocampus has been studied 6, 21, 42 and 90 days after surgery. At 6 and 21 days after operation the postlesion decrease of [(3)H]5-hydroxytryptamine uptake was counter...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(87)90127-6
更新日期:1987-01-01 00:00:00
abstract::Immunoglobulin G (IgG) antibodies against myelin oligodendrocyte glycoprotein (MOG) are detected in the serum of some patients with demyelinating diseases. These patients are known to show repeated clinical episodes of inflammatory demyelinating attacks in the central nervous system. Although the associated pathogenic...
journal_title:Neurochemistry international
pub_type: 杂志文章,评审
doi:10.1016/j.neuint.2018.10.016
更新日期:2019-11-01 00:00:00
abstract::The rat pheochromocytoma cell line PC12 undergoes morphological differentiation into neurone-like cells when exposed to nerve growth factor (NGF). We found that in PC12 cells the enzymatic activity of choline-acetyltransferase and of tyrosine hydroxylase changed very little during NGF exposure, while tyrosine hydroxyl...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/0197-0186(90)90142-g
更新日期:1990-01-01 00:00:00
abstract::P2Y purinergic receptors expressed in neurons and satellite glial cells (SGCs) of the trigeminal ganglion (TG) contribute to inflammatory and neuropathic pain. P2Y14 receptor expression is reported in the spinal cord, dorsal root ganglion (DRG), and TG. In present study, the role of P2Y14 receptor in the TG in inflamm...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2019.104567
更新日期:2019-12-01 00:00:00
abstract::The mechanisms associated with cognitive decline in post-menopausal state driven by loss of ovarian function and reduced estrogen levels are not well understood. The aim of the present study is to investigate the role of mitochondrial dysfunctions in cognitive impairment in post-menopausal state and to evaluate the pr...
journal_title:Neurochemistry international
pub_type: 杂志文章
doi:10.1016/j.neuint.2014.04.011
更新日期:2014-07-01 00:00:00