Abstract:
:Lithium is the simplest therapeutic agent available for the treatment of depression and has been used for over 100 years, yet no definitive mechanism for its effect has been established. Among the proposed mechanisms, two lithium-sensitive signal transduction pathways are active in the brain; these are mediated by glycogen synthase kinase 3beta (GSK-3beta) and inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] signalling. This article describes recent experiments in cell and developmental biology that advance our understanding of how lithium works and it presents new directions for the study of both depression and Alzheimer's disease (AD).
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Williams RS,Harwood AJdoi
10.1016/s0165-6147(99)01428-5subject
Has Abstractpub_date
2000-02-01 00:00:00pages
61-4issue
2eissn
0165-6147issn
1873-3735pii
S0165-6147(99)01428-5journal_volume
21pub_type
杂志文章abstract::Clodronate is a first-generation bisphosphonate used worldwide for antiresorptive therapy for osteoporosis. Although clodronate is analgesic in nature, its mechanism and efficacy were unknown for some time. Recently, clodronate was identified as a selective and potent inhibitor for vesicular nucleotide transporter (VN...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2017.10.007
更新日期:2018-01-01 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::As we have learnt from earlier articles in our series on the pharmacology of excitatory amino acids, neurons and glia express several subtypes of excitatory amino acid receptor, the activation of which increases intracellular free calcium ion concentration. In this sixth article, Mark Mayer and Richard Miller detail t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(90)90254-6
更新日期:1990-06-01 00:00:00
abstract::The use of genetically-engineered mice has identified alpha2- and alpha3-subunit containing GABA(A) receptors as principal contributors to the spinal disinhibition that occurs after inflammation and neuropathic injury. Pharmacological comparison of subtype selective allosteric modulators such as NS11394 and L838417 wi...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2009.06.004
更新日期:2009-09-01 00:00:00
abstract::Opioid receptors are expressed on peripheral sensory nerve endings, cutaneous cells, and immune cells; and local application of opioids is used for the treatment of inflammatory pain in arthritis, burns, skin grafts, and chronic wounds. However, peripherally active opioids can also directly modulate the inflammatory p...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2013.03.006
更新日期:2013-06-01 00:00:00
abstract::Clinical experience with muscarinic agonists in the symptomatic treatment of Alzheimer's disease includes studies of the effects of pilocarpine, arecoline, bethanechol, oxotremorine and RS 86. Although the results are somewhat conflicting, there is evidence that a subgroup of patients may respond with an improvement o...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:
更新日期:1989-12-01 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::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::Pharmacology as a modern science was introduced in China approximately 150 years ago, and has been used since then to study traditional Chinese medicine (TCM). Pharmacology has experienced its own development over this time and continues to provide new tools for the study of TCM. In the present review, three models fo...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.09.004
更新日期:2013-11-01 00:00:00
abstract::There is increasing awareness of the compartmentalization of cAMP signalling--the means by which cAMP levels change in discrete domains of the cell with discrete local consequences. Current developments in understanding the organization of adenylyl cyclases in the plasma membrane are illuminating how the earliest part...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.06.002
更新日期:2006-08-01 00:00:00
abstract::Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and ch...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.12.004
更新日期:2014-03-01 00:00:00
abstract::In the past 20 years we have learned a great deal about GABAA receptor (GABAAR) subtypes, and which behaviors are regulated or which drug effects are mediated by each subtype. However, the question of where GABAARs involved in specific drug effects and behaviors are located in the brain remains largely unanswered. We ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.04.003
更新日期:2018-08-01 00:00:00
abstract::Muscarinic acetylcholine receptor subtypes m1, m3 and m5 couple strongly to phosphatidylinositol turnover and hence to intracellular Ca2+ concentration via pertussis toxin (PTX) sensitive and insensitive G proteins. The m2 and m4 muscarinic receptor subtypes strongly inhibit adenylyl cyclase production via PTX sensiti...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:
更新日期:1989-12-01 00:00:00
abstract::The discovery of neuropeptides as signaling molecules with paracrine or hormonal regulatory functions has led to trailblazing advances in physiology and fostered the characterization of numerous neuropeptide-binding G protein-coupled receptors (GPCRs) as potential drug targets. The impact on human health has been trem...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.05.009
更新日期:2015-09-01 00:00:00
abstract::Adenosine is an endogenous nucleoside that modulates many physiological processes. Its actions are mediated by interaction with specific cell membrane receptors. Four subtypes of adenosine receptor have been cloned: A1, A2A, A2B and A3. Significant advancement has been made in our understanding of the molecular pharma...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01179-1
更新日期:1998-04-01 00:00:00
abstract::The GPR119 receptor is expressed predominantly in pancreatic β cells and in enteroendocrine cells. It is a major target for the development of anti-diabetic drugs that through GPR119 activation may stimulate both insulin and GLP-1 release. GPR119 can be activated by oleoylethanolamide and several other endogenous lipi...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2012.03.014
更新日期:2012-07-01 00:00:00
abstract::The GABAA receptor belongs, along with the nicotinic acetylcholine receptor, the glycine receptor and the 5-HT3 receptor, to a family of homologous transmitter-gated ion channels mediating fast synaptic transmission. Many classes of drug interact with the GABAA receptor, which is the major inhibitory ion channel in th...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(97)01118-8
更新日期:1997-11-01 00:00:00
abstract::Traditional African medicine (TAM) is a shorthand reference to indigenous forms of healing that are practiced all over Africa. Although TAM is based on the accumulated experience of ancient Africans, its mode of transmission by word-of-mouth has hindered emergence of a generally accepted theory and hence of the system...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(99)01406-6
更新日期:1999-12-01 00:00:00
abstract::During the past decade remarkable progress in molecular genetics and the possibility of manipulating cells so that the expression of genes can directly 'report' on drug activity has produced major changes in drug development strategies. The recent description and pharmacological validation of reporter mice for in vivo...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2004.04.007
更新日期:2004-06-01 00:00:00
abstract::Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29bp) in mammalian cells has existed for several years. Two recent articles demonstrate that short sequences within long double-stranded (ds)RNAs frequently cause undesirable OTEs in cultured Drosophila cells. These results reveal the...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2007.02.009
更新日期:2007-04-01 00:00:00
abstract::Protein kinase Calpha (PKCalpha) is a member of the AGC (which includes PKD, PKG and PKC) family of serine/threonine protein kinases that is widely expressed in mammalian tissues. It is closely related in structure, function and regulation to other members of the protein kinase C family, but has specific functions wit...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2009.10.006
更新日期:2010-01-01 00:00:00
abstract::Molecular forms of acetylcholinesterase exhibit tissue-specific distribution, and each form is anchored to the cell surface via a particular post-translational modification of the catalytic subunit. Nibaldo Inestrosa and Alejandra Perelman review evidence that heparan sulphate proteoglycans are the extracellular matri...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(89)90067-9
更新日期:1989-08-01 00:00:00
abstract::Endothelial-dependent relaxation of vascular smooth muscle cells evoked by a number of agonists, including cholinomimetics and substance P, is often accompanied by an increase (repolarization and/or hyperpolarization) in the membrane potential. This change in membrane potential appears predominantly to reflect the act...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)88969-5
更新日期:1995-01-01 00:00:00
abstract::Release of cytotoxic granule proteins from activated eosinophil granules is considered to be a key pathogenic mechanism in eosinophilic diseases. Degenerated eosinophils and extracellular eosinophil granules have been repeatedly depicted. The present overview describes evidence that eosinophil lysis and distribution o...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(97)01042-0
更新日期:1997-04-01 00:00:00
abstract::Neuromodulin is a neurospecific calmodulin binding protein that is implicated in neurite extension, axonal elongation and long-term potentiation. Yuechueng Liu and Daniel Storm propose that neuromodulin binds and concentrates calmodulin on growth cone membranes and that stimulation of protein kinase C releases high lo...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(90)90195-e
更新日期:1990-03-01 00:00:00
abstract::Many diseases result from defects in cell signaling. Achieving an in-depth understanding of the complex mechanisms by which cells transduce extracellular signals into cellular responses in both normal and diseased systems is a crucial step in the discovery of more effective drugs to treat human diseases. Traditional a...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01448-6
更新日期:2000-04-01 00:00:00
abstract::Multidrug resistance is associated with the overexpression of P-glycoprotein, a membrane glycoprotein. The mechanism by which P-glycoprotein confers to cells the capacity to resist cytotoxic attack by structurally unrelated drugs has remained difficult to decipher. However, the recent functional expression of this gro...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(94)90322-0
更新日期:1994-07-01 00:00:00
abstract::Oxidative stress is a key pathologic factor in neurodegenerative diseases such as Alzheimer and Parkinson diseases (AD, PD). The failure of free-radical-scavenging antioxidants in clinical trials pinpoints an urgent need to identify and to block major sources of oxidative stress in neurodegenerative diseases. As a maj...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2012.03.008
更新日期:2012-06-01 00:00:00
abstract::Controversy over the meaning of pharmacological parameters often arises because of a lack of appreciation of different hierarchical levels of analysis. In a recent letter in Trends in Pharmacological Sciences, Zhang and Kavana [1] concluded that my two-state model for allosterism lacks cooperativity, even though Figur...
journal_title:Trends in pharmacological sciences
pub_type: 评论,信件
doi:10.1016/j.tips.2016.06.001
更新日期:2016-08-01 00:00:00
abstract::Successful biologics must satisfy multiple properties including activity and particular physicochemical features that are globally defined as developability. These multiple properties must be simultaneously optimized in a very broad design space of protein sequences and buffer compositions. In this context, artificial...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2020.12.004
更新日期:2021-01-23 00:00:00