Abstract:
:Recent advances in schizophrenia (SZ) research indicate that the telencephalic gamma-aminobutyric acid (GABA)ergic neurotransmission deficit associated with this psychiatric disorder probably is mediated by the hypermethylation of the glutamic acid decarboxylase 67 (GAD(67)), reelin and other GABAergic promoters. A pharmacological strategy to reduce the hypermethylation of GABAergic promoters is to induce a DNA-cytosine demethylation by altering the chromatin remodeling with valproate (VPA). When co-administered with VPA, the clinical efficacy of atypical antipsychotics is enhanced. This prompted us to investigate whether this increase in drug efficacy is related to a modification of GABAergic-promoter methylation via chromatin remodeling. Our previous and present results strongly indicate that VPA facilitates chromatin remodeling when it is associated with clozapine or sulpiride but not with haloperidol or olanzapine. This remodeling might contribute to reelin- and GAD(67)-promoter demethylation and might reverse the GABAergic-gene-expression downregulation associated with SZ morbidity.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Guidotti A,Dong E,Kundakovic M,Satta R,Grayson DR,Costa Edoi
10.1016/j.tips.2008.10.010subject
Has Abstractpub_date
2009-02-01 00:00:00pages
55-60issue
2eissn
0165-6147issn
1873-3735pii
S0165-6147(08)00251-4journal_volume
30pub_type
杂志文章abstract::Delayed biochemical changes play an important role in tissue damage resulting from traumatic injuries to the central nervous system. Identification of such 'secondary' injury factors has led to the development of various pharmacological strategies aimed at limiting this progressive tissue destruction. In this review, ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(92)90013-v
更新日期:1992-01-01 00:00:00
abstract::Drugs that cause liver injury often 'stress' mitochondria and activate signal transduction pathways important in determining cell survival or death. In most cases, hepatocytes adapt to the drug-induced stress by activating adaptive signaling pathways, such as mitochondrial adaptive responses and nuclear factor erythro...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.01.009
更新日期:2013-04-01 00:00:00
abstract::Humans are exposed to mixtures of chemicals, rather than to individual chemicals. From a public health point of view, it is most relevant to answer the question of whether or not the components in a mixture interact in a way that results in an increase in their overall effect compared with the sum of the effects of th...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01720-x
更新日期:2001-06-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a pulmonary inflammatory disease that is caused by cigarette smoke. The main characteristic of COPD is the continued inflammation caused by the sustained influx of macrophages and neutrophils into the lung. Recent studies have shed light on how these cells are attracted ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2006.09.003
更新日期:2006-11-01 00:00:00
abstract::Daily rhythms in behavior, physiology, and metabolism are an integral part of homeostasis. These rhythms emerge from interactions between endogenous circadian clocks and ambient light-dark cycles, sleep-activity cycles, and eating-fasting cycles. Nearly the entire primate genome shows daily rhythms in expression in ti...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.07.003
更新日期:2018-09-01 00:00:00
abstract::Salvinorin A, a neoclerodane diterpene, is the most potent naturally occurring hallucinogen known and rivals the synthetic hallucinogen lysergic acid diethylamide in potency. Recently, the molecular target of salvinorin A was identified as the kappa opioid receptor (KOR). Salvinorin A represents the only known non-nit...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/S0165-6147(03)00027-0
更新日期:2003-03-01 00:00:00
abstract::The metabotropic glutamate (mGlu) receptors are a family of G-protein-coupled receptors (GPCRs) that regulate cell physiology throughout the nervous system. The potential of mGlu receptors as therapeutic targets has been bolstered by current research that has provided insight into the diverse modes of mGlu activation ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2019.02.006
更新日期:2019-04-01 00:00:00
abstract::It has been suggested that G protein-coupled receptors can act as proton transporters, with the activated G protein-coupled receptor transporting H+ across the membrane from the extracellular side to the cytoplasm. In this article, Paul Nederkoorn, Henk Timmerman and Gabriëlle Donné-Op den Kelder summarize the various...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)89008-2
更新日期:1995-05-01 00:00:00
abstract::Apoptosis plays a key role in tumour biology, and the induction of apoptosis forms a cornerstone of most anticancer therapies. New developments in nuclear magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) have taken these techniques far beyond their original roles as the workhorses of structur...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/S0165-6147(03)00032-4
更新日期:2003-03-01 00:00:00
abstract::Much regarding the engagement of the G(12) family of heterotrimeric G proteins (G(12) and G(13)) by agonist-activated receptors remains unclear. For example, the identity of receptors that couple unequivocally to G(12) and G(13) and how signals are allocated among these and other G proteins remain open questions. Part...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.01.007
更新日期:2005-03-01 00:00:00
abstract::Until recently, release studies have failed to indicate the existence of autoreceptors on motor nerves. Ignaz Wessler now reports on a refinement of the technique - the measurement of newly synthesized [3H]acetylcholine released from the phrenic nerve - which provides clear evidence in support of release-modulating au...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(89)90208-3
更新日期:1989-03-01 00:00:00
abstract::The genotoxicity of the most potent carcinogen in cigarette smoke [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] is dependent on the relationship between its activation by cytochrome P450 enzymes and its detoxification by carbonyl reduction to NNK alcohol (NNAL) followed by glucuronidation. Recently, '11 beta-...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(97)01090-0
更新日期:1997-08-01 00:00:00
abstract::Several clinical studies document a greater discrimination between asthmatic and healthy subjects in bronchial responsiveness to a range of stimuli such as cold air, distilled water and sodium metabisulphite, than to conventional bronchoconstrictor agonists including histamine and methacholine. One of the mechanisms t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01261-9
更新日期:1998-11-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is an incurable disease that arises from the progressive loss of motoneurons. Even when caused by a single gene defect, as in the case of mutations in the enzyme Cu-Zn superoxide dismutase (SOD1), ALS is the result of a complex cascade that involves crosstalk among motoneurons, glia...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.03.009
更新日期:2006-05-01 00:00:00
abstract::Receptors that are coupled to the production of inositol (1,4,5)-trisphosphate cause an increase in cytosolic free Ca2+ concentration as a consequence of both Ca2+ mobilization from intracellular stores and Ca2+ influx through the plasma membrane. Although this latter phenomenon appears attributable to the activation ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(94)90282-8
更新日期:1994-03-01 00:00:00
abstract::The enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate species either to DNA synthesis or to homocysteine (Hcy) remethylation. The common MTHFR C677T polymorphism affects the activity of the enzyme and hence folate distribution. Under conditions of impaired folate status, the homozygous TT genotype has ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01675-8
更新日期:2001-04-01 00:00:00
abstract::Cardiovascular disease remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves epoxyeicosatrienoic acid (EET) and soluble epoxide hydroxylase (sEH) inhibition. sEH is the enzyme that converts EET to its less potent metabolite; therefore...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.08.001
更新日期:2016-11-01 00:00:00
abstract::Discoidin (DS) domains are found in eukaryotic and prokaryotic extracellular and transmembrane multidomain proteins. These small domains play different functional roles and can interact with phospholipids, glycans, and proteins, including collagens. DS domain-containing proteins are often involved in cellular adhesion...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.06.003
更新日期:2016-08-01 00:00:00
abstract::Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2014.07.001
更新日期:2014-09-01 00:00:00
abstract::5-HT(3) receptors are widely distributed in the CNS and PNS where they participate in a variety of physiological processes. Native 5-HT(3) receptors in the CNS display functional and pharmacological heterogeneity, suggesting the existence of multiple receptor subunits. However, recent evidence suggests that of the two...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/S0165-6147(03)00051-8
更新日期:2003-04-01 00:00:00
abstract::Approximately 27 million people are living with a tumour in which the tumour suppressing activity of p53 has been inactivated. In half of these tumours, p53 itself is not mutated but the pathway is partially abrogated. Mechanisms include the overexpression of negative regulators of p53, such as MDM2 and MDM4, and dele...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2010.11.004
更新日期:2011-01-01 00:00:00
abstract::Within five years of discovering endothelin (ET-1) in 1988, the first report of an orally available ET receptor antagonist was published. Within twelve years, bosentan, the first ET receptor antagonist to gain marketing authorization, was made available for the treatment of pulmonary artery hypertension (PAH). Since t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.10.002
更新日期:2007-11-01 00:00:00
abstract::Three 'alpha 1-adrenoceptors' and three 'alpha 2-adrenoceptors' have now been cloned. How closely do these receptors match the native receptors that have been identified pharmacologically? What are the properties of these receptors, and how do they relate to other members of the cationic amine receptor family? Kevin L...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(91)90499-i
更新日期:1991-02-01 00:00:00
abstract::For almost 70 years, children have received stimulants for the treatment of attention deficit hyperactivity disorder [ADHD (initially called hyperkinetic syndrome)], with little understanding of the long-term effects of these drugs on brain development. The maturation and refinement of the brain during childhood and a...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.03.009
更新日期:2005-05-01 00:00:00
abstract::Kinin B1 and B2 receptors are central to the aetiology of pain and inflammation. Constitutive B2 receptors are commonly associated with the acute phase of inflammation and nociception, whereas the inducible B1 receptors are mostly linked to the chronic or persistent phase (or both). Therefore, selective, orally active...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.10.007
更新日期:2006-12-01 00:00:00
abstract::Prospecting the full biodiversity of nature to find leads for new drugs is not necessary. Because finding leads is aimed at identifying biological activity, structure is of secondary importance. Furthermore, although natural chemical diversity might be unrivalled, functional diversity is bound to be considerably less....
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/s0165-6147(02)02007-2
更新日期:2002-05-01 00:00:00
abstract::Gene therapy is a new field of medical research that has great potential to influence the course of treatment of human disease. The lung has been a particularly attractive target organ for gene therapy due to its accessibility and the identification of genetic deficits for a number of lung diseases. Several clinical t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(99)01350-4
更新日期:1999-06-01 00:00:00
abstract::Nearly all molecules known to signal cells via G proteins have been assigned a cloned G-protein-coupled-receptor (GPCR) gene. This has been the result of a decade-long genetic search that has also identified some receptors for which ligands are unknown; these receptors are described as orphans (oGPCRs). More than 80 o...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(99)01366-8
更新日期:1999-09-01 00:00:00
abstract::It has been hypothesized that anxiety disorders play an important role in the initiation and maintenance of alcohol drinking behaviors. However, the molecular mechanisms for the association between anxiety and alcohol abuse are not well understood. Structures of the extended amygdala, particularly the central nucleus ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/S0165-6147(03)00226-8
更新日期:2003-09-01 00:00:00
abstract::Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanisti...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.08.002
更新日期:2016-11-01 00:00:00