Abstract：
:The members of the Cys-loop ligand-gated ion channel (LGIC) gene family play a major role in fast synaptic transmission, and these receptors represent an important class of targets for therapeutic agents. Each member of this gene family is a pentameric complex containing one or more different subunits, and a large number of subunits for each member have been identified. This large number of subunits could give rise to a bewildering array of possible subunit compositions and spatial arrangements within a single complex, not all of which may occur in vivo. Heterologous expression systems have been used to create specific combinations of individual subunits to mimic naturally occurring receptors. However, this approach is not without its problems. In this issue of Molecular Pharmacology, Groot-Kormelink et al. (page 559) describe a method for constructing "concatameric" receptors, in which five individual subunits are arranged in a predetermined order connected by a flexible linker. Expression of this construct results in the formation of receptors with a unique, predefined subunit stoichiometry and subunit arrangement within the receptor complex. Receptors formed from this construct are fully functional and have properties essentially identical to those formed from individual subunits. The application of this very general approach to other members of the LGIC family should markedly enhance our ability to understand how subunit composition influences receptor function, as well as provide a means for the expression of receptors of predefined subunit composition and arrangement as tools for the development of novel selective pharmacological and therapeutic agents.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
White MMdoi
10.1124/mol.105.020727keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
407-10issue
2eissn
0026-895Xissn
1521-0111pii
mol.105.020727journal_volume
69pub_type
评论,杂志文章,评审abstract：:Melanocortins (MCs) have various physiological actions on the brain. The recent cloning of neural MC receptors opened new avenues to study the effects of these neuropeptides on the nervous system. Here we investigated the structure-activity relationships (SARs) of peptides derived from adrenocorticotropic hormone (ACT...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:The phosphorylation of μ-opioid receptors (MOPRs) by G protein-coupled receptor kinases (GRKs), followed by arrestin binding, is thought to be a key pathway leading to desensitization and internalization. The present study used the combination of intracellular and whole-cell recordings from rats and mice, as well as l...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.076208
更新日期：2012-03-01 00:00:00
abstract：:The effects of the dihydropyridine calcium channel agonist Bay K 8644 on indo-1-loaded Jurkat human leukemia T lymphocytes was assessed by flow cytometry. Bay K 8644 from 10(-9) to 10(-4) M caused a dose-dependent rise in the intracellular free Ca concentration, an effect that was not mimicked by the dihydropyridine C...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
abstract：:Regulator of G protein signaling (RGS) proteins are negative modulators of G protein signaling that have emerged as promising drug targets to improve specificity and reduce side effects of G protein-coupled receptor-related therapies. Several small molecule RGS protein inhibitors have been identified; however, enhanci...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/molpharm.120.000061
更新日期：2020-12-01 00:00:00
abstract：:ATP-sensitive K(+) channels are closed by the hypoglycemic sulfonylureas like glibenclamide (GBC) and activated by a class of vasorelaxant compounds, the K(+) channel openers. These channels are octamers of Kir6.x and sulfonylurea receptor (SUR) subunits with 4:4 stoichiometry. The properties of the opener-sensitive K...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
abstract：:(6R)-5,6,7,8-Tetrahydrobiopterin (BH4), which is synthesized intracellularly from GTP, caused a concentration-dependent increase in rat pheochromocytoma (PC12) cell proliferation when added exogenously. Incubation with sepiapterin, which is converted enzymatically to BH4 within cells, also increased PC12 cell prolifer...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:G protein-coupled receptors are sensors that interact with a large variety of elements, including photons, ions, and large proteins. Not surprisingly, these receptors participate in the numerous normal physiologic processes that we refer to as health and in its perturbations that constitute disease. It has been estima...
journal_title：Molecular pharmacology
pub_type：
doi：10.1124/mol.116.106062
更新日期：2016-11-01 00:00:00
abstract：:The midbrain periaqueductal gray (PAG) is involved in organizing behavioral responses to threat, stress, and pain. These PAG functions are modulated by cholinergic agents. In the present study, we examined the cholinergic modulation of synaptic transmission in the PAG using whole-cell voltage-clamp recordings from rat...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.045872
更新日期：2008-11-01 00:00:00
abstract：:Nicotine can enhance working memory and attention. Activation of both alpha7 and beta2(*) nicotinic acetylcholine receptors (nAChRs) in the prefrontal cortex (PFC) has been implicated in these processes. The ability of presynaptic nAChRs to modulate neurotransmitter release, notably glutamate release, is postulated to...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.046623
更新日期：2008-08-01 00:00:00
abstract：:Expression of the angiotensin II type 1 receptor (AT1-R) mRNA in vascular smooth muscle cells (VSMC) is down-regulated by a variety of agonists, including growth factors, agonists of Galphaq protein-coupled receptors, and activators of adenylyl cyclase. To determine whether cAMP-dependent protein kinases (PKA) partici...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.54.3.514
更新日期：1998-09-01 00:00:00
abstract：:Extracellular ATP activates two distinct types of P2 purinoreceptor-mediated signaling pathways in macrophages, 1) the rapid formation of nonselective pores/channels in the plasma membrane and 2) a guanine nucleotide-binding protein-dependent stimulation of phosphotidylinositol-specific phospholipase C, with subsequen...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:P-glycoprotein, an ATP-driven efflux pump, regulates permeability of the blood-brain barrier (BBB). Sphingolipids, endogenous to brain tissue, influence inflammatory responses and cell survival in vitro. Our laboratory has previously shown that sphingolipid signaling by sphingosine 1-phosphate decreases basal P-glycop...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107169
更新日期：2017-04-01 00:00:00
abstract：:We examined the effect of trichosporin-B-III, an alpha-aminoisobutyric acid-containing antibiotic peptide consisting of 19 amino acid residues and a phenylalaninol, on catecholamine secretion from cultured bovine adrenal chromaffin cells. Incubation of the cells with trichosporin-B-III (3-20 microM) caused an increase...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:We describe the nucleic acid sequence encoding a human 5-hydroxytryptamine1D (5-HT1D) serotonin receptor and some of the functional characteristics of the gene product. The receptor gene was isolated by hybridization to a probe based on a canine thyroid cDNA (called RDC4) previously isolated by others and believed to ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Batrachotoxin (BTX), from South American frogs of the genus Phyllobates, irreversibly activates voltage-gated sodium channels. Previous work demonstrated that a phenylalanine residue approximately halfway through pore-lining transmembrane segment IVS6 is a critical determinant of channel sensitivity to BTX. In this st...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.4.905
更新日期：2002-04-01 00:00:00
abstract：:TWIK-related K+ channel TREK1, a background leak K+ channel, has been strongly implicated as the target of several general and local anesthetics. Here, using the whole-cell and single-channel patch-clamp technique, we investigated the effect of lidocaine, a local anesthetic, on the human (h)TREK1 channel heterologousl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.056838
更新日期：2009-10-01 00:00:00
abstract：:In a previous report we described the use of flunitrazepam as a photoaffinity label to monitor the turnover of the gamma-aminobutyric acid/benzodiazepine receptor complex in primary brain and spinal cord cell cultures [Science (Wash. D. C.) 226:857-860 (1984)]. In the present communication we have extended our studies...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
abstract：:Diltiazem is a widely prescribed Ca2+ antagonist drug for cardiac arrhythmia, hypertension, and angina pectoris. Using the ancestral CaV channel construct CaVAb as a molecular model for X-ray crystallographic analysis, we show here that diltiazem targets the central cavity of the voltage-gated Ca2+ channel underneath ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.119.117531
更新日期：2019-10-01 00:00:00
abstract：:Rat liver and brain membrane alpha 1-adrenergic receptors were purified greater than 500-fold by successive chromatographic steps using heparin-agarose, an affinity matrix constructed by coupling a novel derivative of the alpha 1-selective antagonist prazosin to Affigel-102 and wheat germ agglutinin-agarose. Several l...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:To study behavior of activated G(alpha)(s) in living cells, green fluorescent protein (GFP) was inserted within the internal amino acid sequence of G(alpha)(s) to generate a G(alpha)(s)-GFP fusion protein. The fusion protein maintained a bright green fluorescence and was identified by immunoblotting with antibodies ag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.2.352
更新日期：2002-02-01 00:00:00
abstract：:Ca2-dependent protein phosphorylations activated by calmodulin or phospholipid were studied using selective inhibitors. Both protein phosphorylations were inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives. Kinetic analysis indicated that the primary effect of these agents was me...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
abstract：:The binding of two anthranilic acid derivatives, glafenic and floctafenic acids, to human erythrocytes and plasma proteins has been investigated in vitro by equilibrium dialysis. Despite their close chemical structures it was shown that the binding of the two compounds to serum albumin, lipoproteins, and erythrocytes ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
abstract：:We cloned and expressed a human metabotropic glutamate receptor 1 alpha (HmGluR1 alpha) in a novel cell line. The human mGluR1 alpha cDNA was found to be 86% identical to rat mGluR1 alpha, and the predicted protein sequence was found to be 93% identical to rat mGluR1 alpha. We expressed HmGluR1 alpha in AV12-664, an a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:The delta family of ionotropic glutamate receptors consists of glutamate delta-1 (GluD1) and glutamate delta-2 receptors. We have previously shown that GluD1 knockout mice exhibit features of developmental delay, including impaired spine pruning and switch in the N-methyl-D-aspartate receptor subunit, which are releva...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.104786
更新日期：2016-08-01 00:00:00
abstract：:Controlled inhibition of brain acetyl- and butyrylcholinesterases (AChE and BChE, respectively) and of monoamine oxidase-B (MAO-B) may slow neurodegeneration in Alzheimer's and Parkinson's diseases. It was postulated that certain carbamate esters would inhibit AChE and BChE with the concomitant release in the brain of...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.033928
更新日期：2007-06-01 00:00:00
abstract：:G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107854
更新日期：2017-09-01 00:00:00
abstract：:Bufuralol 1'-hydroxylation is a prototypical reaction catalyzed by cytochrome P450 (P450) 2D6, an enzyme known to show debrisoquine/sparteine-type genetic polymorphism in humans. In the present study we further examined the roles of several human P450 enzymes, as well as P450 2D6, in the hydroxylation of (+/-)-bufural...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:Glucose utilization in isolated islets of Langerhans of the rat was determined by measuring the conversion of [5-3H]glucose (10 mM) to 3H2O. The alpha 2-adrenoceptor agonists clonidine, epinephrine, and norepinephrine in the presence of the alpha 1-adrenoceptor antagonist prazosin and the beta-adrenoceptor antagonist ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
abstract：:Liver homeostasis is achieved by the removal of diseased and damaged hepatocytes and their coordinated replacement to maintain a constant liver cell mass. Cirrhosis, viral hepatitis, and toxic drug effects can all trigger apoptosis in the liver as a means of removing the unwanted cells, and the Fas "death receptor" pa...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.005223
更新日期：2005-03-01 00:00:00
abstract：:The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel reco...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
