Abstract:
:It has taken 17 years from the first identification of a voltage-gated Ca2+ channel (CaV) beta-subunit as a band on a gel following purification of skeletal muscle dihydropyridine (DHP) receptors in 1987 to the publication of key information on the structures of Ca2+ channel beta-subunits. Three recent X-ray crystallographic studies have now solved the structures of the core domains of three Ca2+ channel beta-subunits. In this article, the properties of these cytoplasmic auxiliary subunits will first be summarized. Then the CaVbeta structures and the information they provide regarding how these proteins interact with the CaValpha1 subunit will be discussed and the possible implications of these new data for G-protein modulation of Ca2+ channels will be examined.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Richards MW,Butcher AJ,Dolphin ACdoi
10.1016/j.tips.2004.10.008subject
Has Abstractpub_date
2004-12-01 00:00:00pages
626-32issue
12eissn
0165-6147issn
1873-3735pii
S0165-6147(04)00286-Xjournal_volume
25pub_type
杂志文章,评审abstract::Recently, nicotinic acid adenine dinucleotide phosphate (NAADP) has been shown, using different techniques, to mobilize intracellular Ca2+ stores in invertebrate, lower vertebrate, plant and mammalian cells. This endogenous molecule might play an atypical role in Ca2+ signalling by coordinating the responses of other ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)01990-8
更新日期:2002-04-01 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::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::Within the past six months, isolation of cDNA or genomic clones has been reported for three 5-HT receptors, the 5-HT1C, 5-HT1A and 5-HT2 subtypes. As members of the G protein receptor superfamily, all three 5-HT receptor clones encode single-subunit proteins containing approximately 450 amino acids arrayed as seven in...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(89)90080-1
更新日期:1989-02-01 00:00:00
abstract::The histamine H3 receptor was discovered 15 years ago, and many potent and selective H3 receptor agonists and antagonists have since been developed. Currently, much attention is being focused on the therapeutic potential of H3 receptor ligands. In this review, Rob Leurs, Patrizio Blandina, Clark Tedford and Henk Timme...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01201-2
更新日期:1998-05-01 00:00:00
abstract::In the conventional view, GABA acts at either ionotropic GABAA or metabotropic GABAB receptors. Recently, novel ionotropic GABA receptors that are composed of rho-subunits have been identified in the vertebrate retina. These bicuculline- and baclofen-insensitive GABA receptors are frequently called GABAC, following an...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(99)01413-3
更新日期:2000-01-01 00:00:00
abstract::Five subtypes of muscarinic acetylcholine receptors have been identified in mammalian tissues, but the selectivity of ligands that are active at these receptors is low. It is possible, however, that selective compounds may be developed by targeting their allosteric site(s). Important new insights into the mechanism of...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)89023-9
更新日期:1995-06-01 00:00:00
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 ph...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2008.10.010
更新日期:2009-02-01 00:00:00
abstract::Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice wit...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2010.12.005
更新日期:2011-03-01 00:00:00
abstract::Heat shock proteins (HSPs) constitute a large family of proteins involved in protein folding and maturation whose expression is induced by heat shock or other stressors. The major groups are classified based on their molecular weights and include HSP27, HSP40, HSP60, HSP70, HSP90, and large HSPs. HSPs play a significa...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.11.009
更新日期:2017-03-01 00:00:00
abstract::During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial ce...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.02.008
更新日期:2016-05-01 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::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::Annexin A1 (ANXA1) is an endogenous protein known to have potent anti-inflammatory properties in the peripheral system. It has also been detected in the brain, but its function there is still ambiguous. In this review, we have, for the first time, collated the evidence currently available on the function of ANXA1 in t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.12.003
更新日期:2008-03-01 00:00:00
abstract::The British Pharmacological Society (BPS) is currently celebrating its 75th anniversary. It is therefore a young society compared with some other biomedical societies and particularly when compared with the origins of the oldest learned societies. In this article, I briefly review the origins of learned societies and ...
journal_title:Trends in pharmacological sciences
pub_type: 历史文章,杂志文章
doi:10.1016/j.tips.2006.01.001
更新日期:2006-03-01 00:00:00
abstract::The efficacy of the powerful CRISPR-Cas9 genome-editing platform depends on DNA repair activities in the cells being targeted. Two new papers show that the low efficiency of targeting in some primary human cell lines is the result of p53-dependent cell arrest in response to the Cas9-induced break. This limitation must...
journal_title:Trends in pharmacological sciences
pub_type: 评论,杂志文章
doi:10.1016/j.tips.2018.06.005
更新日期:2018-09-01 00:00:00
abstract::Plants have been the predominant source of medicines throughout the vast majority of human history, and remain so today outside of industrialized societies. One of the most versatile in terms of its phytochemistry is cannabis, whose investigation has led directly to the discovery of a unique and widespread homeostatic...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.04.005
更新日期:2016-07-01 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::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::From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one o...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2010.08.006
更新日期:2010-12-01 00:00:00
abstract::Transcription factors comprise just over 7% of the human proteome and serve as gatekeepers of cellular function, integrating external signal information into gene expression programs that reconfigure cellular physiology at the most basic levels. Surface-initiated cell signaling pathways converge on transcription facto...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2013.11.005
更新日期:2014-02-01 00:00:00
abstract::The myeloid-derived suppressor cell (MDSC) is the 'queen bee' of the tumor microenvironment. MDSCs protect the cancer from the patient's immune system, make the tumor resistant to immunotherapy, and allow the tumor to thrive while the patient withers away. Eliminating MDSCs should improve response rates to cancer ther...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.10.008
更新日期:2019-01-01 00:00:00
abstract::Sulfoconjugation of drugs and small xenobiotic and endogenous compounds in human tissues is primarily catalysed by cytosolic forms of sulfotransferase. In most instances, sulfate conjugation is associated with a decrease in the biological activity and an increase in the excretion of the sulfated compounds. However, su...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(91)90566-b
更新日期:1991-07-01 00:00:00
abstract::The therapeutic advantage of reducing the activity of interleukin 1 (IL-1) resides in preventing its deleterious biological effects without interfering with homeostasis. As such, methods attempting to block the production or activity of IL-1 have now entered clinical trials. For example, IL-1 induction of prostaglandi...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(93)90200-4
更新日期:1993-05-01 00:00:00
abstract::14-3-3 Proteins enact a range of cellular functions through protein-protein interactions (PPIs) with client proteins. Kaplan and colleagues recently demonstrated that a semisynthetic compound was able to selectively stabilize or disrupt specific interactions, depending on the binding partner. This finding presents an ...
journal_title:Trends in pharmacological sciences
pub_type: 评论,杂志文章
doi:10.1016/j.tips.2020.05.001
更新日期:2020-07-01 00:00:00
abstract::Seven-transmembrane receptors are prototypic allosteric proteins with the ability to adopt numerous conformations, many of which interact with cellular partners to initiate cellular biochemical processes. Defining efficacy as the ability of ligands to stabilize some of these conformations (which, in turn, possess phys...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.06.009
更新日期:2007-08-01 00:00:00
abstract::Pharmacology training in Canada was initiated at McGill University in Montréal in 1824, and there are now 17 pharmacology departments in Canada offering graduate training to more than 500 students. In this article, Gerald Marks reviews the growth of pharmacology in Canada since the early 19th century in both academic ...
journal_title:Trends in pharmacological sciences
pub_type: 历史文章,杂志文章
doi:10.1016/0165-6147(94)90312-3
更新日期:1994-07-01 00:00:00
abstract::Tissue factor (TF) is the cellular receptor and cofactor for blood coagulation factor VII (FVII). Exposure of flowing blood to cells that express TF leads to the initiation of blood coagulation. A recent study of mice expressing low levels of TF has demonstrated the importance of TF and FVII in maintaining adequate ha...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/S0165-6147(03)00121-4
更新日期:2003-06-01 00:00:00
abstract::A diet low in carbohydrates helps to reduce the amount of ingested calories and to maintain a healthy weight. With this in mind, food and beverage companies have reformulated a large number of their products, replacing sugar or high fructose corn syrup with several different types of zero-calorie sweeteners to decreas...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2011.06.007
更新日期:2011-11-01 00:00:00
abstract::Hypertension is prevalent and affects approximately 1 in every 4 adults in the Western world. Although many drugs are effective in treating hypertension, an individual's response to treatment is unpredictable. Pharmacogenetics holds the promise of becoming a tool to predict this response but obstacles and shortcomings...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2005.07.008
更新日期:2005-09-01 00:00:00