Abstract：
:Signaling by G-protein-coupled receptors is often considered a uniform process, whereby a homogeneously activated proportion of randomly distributed receptors are activated under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, the example of rhodopsin with its strictly local single-quantum mode of function shows that homogeneity in space and time cannot be a general property of G-protein-coupled systems. Recent work has now revealed many other systems where such simplicity does not prevail. Instead, a plethora of mechanisms allows much more complex patterns of receptor activation and signaling: different mechanisms of protein-protein interaction; temporal changes under nonequilibrium conditions; localized receptor activation; and localized second messenger generation and degradation-all of which shape receptor-generated signals and permit the creation of multiple signal types. Here, we review the evidence for such pleiotropic receptor signaling in space and time.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Lohse MJ,Hofmann KPdoi
10.1124/mol.115.100248subject
Has Abstractpub_date
2015-09-01 00:00:00pages
572-8issue
3eissn
0026-895Xissn
1521-0111pii
mol.115.100248journal_volume
88pub_type
杂志文章,评审abstract：:Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels encoded by the Slo1 gene are ubiquitously expressed, and they play a role in regulation of many cell types. In excitable cells, BK(Ca) channels and voltage-activated Ca(2+) channels often form functional complexes that allow the cytoplasmic domains of BK(Ca) ch...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.040733
更新日期：2008-02-01 00:00:00
abstract：:The aryl hydrocarbon receptor (AHR) binds planar aromatic compounds and up-regulates the transcription of a battery of xenobiotic-metabolizing enzymes. To identify proteins involved in the biosynthesis of endogenous AHR ligands, we screened extracts of various mouse tissues for AHR signaling activity. We found heart e...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.3.550
更新日期：2003-09-01 00:00:00
abstract：:Typical equilibrium binding experiments cannot be quantitatively analyzed on the basis of classical mathematical equations when the receptor concentration is so high that a significant fraction of the added radioligand concentration is in the bound form. In this paper, the appropriate equations are derived and used in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
abstract：:Several novel phenylaminotetralins (PATs) cause functional changes in brain that are associated with binding to saturable, high affinity sites that are not identical to any known central nervous system receptor. These PATs were tested for their ability to cause receptor-mediated functional effects on tyrosine hydroxyl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：:The seven-transmembrane receptor Smoothened (Smo) is the major component involved in signal transduction of the Hedgehog (Hh) morphogens. Smo inhibitors represent a promising alternative for the treatment of several types of cancers linked to abnormal Hh signaling. Here, on the basis of experimental data, we generated...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.065102
更新日期：2010-10-01 00:00:00
abstract：:Cadmium is a dangerous metal distributed widely in the environment. Members of our laboratory recently identified the ZIP8 transporter protein, encoded by the mouse Slc39a8 gene, to be responsible for genetic differences in response to cadmium damage of the testis. Stable retroviral infection of the ZIP8 cDNA in mouse...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.024521
更新日期：2006-07-01 00:00:00
abstract：:Small-molecule restoration of wild-type structure and function to mutant p53 (so-called mutant reactivation) is a highly sought-after goal in cancer drug development. We previously discovered that small-molecule zinc chelators called zinc metallochaperones (ZMCs) reactivate mutant p53 by restoring zinc binding to zinc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107409
更新日期：2017-06-01 00:00:00
abstract：:The gamma-aminobutyric acid(A) (GABA(A)) receptor contains a binding site (or sites) for benzodiazepines and related ligands. Previous studies have shown that the residue occupying position 101 (rat numbering) of the alpha subunit is particularly important in determining how some of these compounds interact with the r...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:An investigation of the conformational profiles of two cyclic delta-selective opioid peptides, [D-Pen2,D-Pen5]-enkephalin and [D-Pen2,L-Pen5]-enkephalin, has been made. The methods and procedures used are more extensive and systematic than those previously reported, involving a combination of nested grid rotations, cy...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels play an important role in the regulation of cell physiology in a wide variety of excitable and nonexcitable tissues. Filamin A is a conserved and ubiquitous actin-binding protein that forms perpendicular actin cross-links and contributes to changes in cell shap...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.038026
更新日期：2007-09-01 00:00:00
abstract：:Opioid analgesics are used extensively in the management of pain. Although the clinically effective opioids bind with high affinity to the mu-opioid receptor, studies have suggested that the delta-opioid agonists might represent more ideal analgesic agents, with fewer side effects. A limitation to opiate effectiveness...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.2.272
更新日期：1997-08-01 00:00:00
abstract：:Intracellular recordings of membrane potassium current were made from rat locus coeruleus in vitro. The effects of agonists at mu-opioid receptors were studied on neurons from rats that had been chronically treated with morphine; these were compared with actions on neurons from control rats. Tolerance to the opioid-in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-11-01 00:00:00
abstract：:The human mu-opioid receptor (HmuOR) is a G-protein coupled receptor that mediates analgesia, euphoria and other important central and peripheral neurological functions. In this study, we found in a yeast two-hybrid screen that a protein kinase C-interacting protein (PKCI) specifically interacts with the C terminus of...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.66.5.
更新日期：2004-11-01 00:00:00
abstract：:The thiazolidinediones are a class of antidiabetic compounds that increase the sensitivity of target tissues to insulin. An earlier study has shown that these compounds enhance the insulin-stimulated differentiation of 3T3-L1 cells and up-regulate expression of differentiation-dependent genes. We have observed that th...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:We determined the effect of flufenamic acid (FFA) and related derivatives on gap junction channel currents, applying the dual whole-cell patch-clamp technique to pairs of N2A neuroblastoma cells transfected with various connexins. FFA reduced gap junction channel currents in a reversible and concentration-dependent ma...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.6.1389
更新日期：2003-06-01 00:00:00
abstract：:The chemical reaction of 1,4-benzoquinone with glutathione results in the formation of adducts that exhibit increasing degrees of glutathione substitution. Purification of these adducts and analysis by 1H and 13C nuclear magnetic resonance spectroscopy revealed the products of the reaction to be 2-(glutathion-S-yl)hyd...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:G protein-coupled receptor kinases (GRKs) play a key role in the process of receptor homologous desensitization. In the present study, we address the question of whether a variety of receptors coupled to different G protein subtypes and naturally expressed on the same cell are selectively regulated by GRK2. The signal...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.56.2.316
更新日期：1999-08-01 00:00:00
abstract：:A functional interaction between peroxisome proliferator-activated receptor alpha (PPARalpha) and components of the circadian clock has been suggested, but whether these transcriptional factors interact to regulate the expression of their target genes remains obscure. Here we used a PPARalpha ligand, bezafibrate, to s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.064402
更新日期：2010-07-01 00:00:00
abstract：:Nafazatrom, an antithrombotic and antimetastatic agent containing a pyrazolone functionality, is a reducing substrate for the peroxidase activity of prostaglandin H (PGH) synthase. Nafazatrom inhibits the hydroperoxide-dependent oxidation of phenylbutazone, stimulates the reduction of 15-hydroperoxy-5,8,11,13-eicosate...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
abstract：:bTREK-1 K(+) channels set the resting membrane potential of bovine adrenal zona fasciculata (AZF) cells and function pivotally in the physiology of cortisol secretion. Adrenocorticotropic hormone controls the function and expression of bTREK-1 channels through signaling mechanisms that may involve cAMP and downstream ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.061861
更新日期：2010-03-01 00:00:00
abstract：:Previous studies indicated that activation of alpha 1-adrenergic receptors in BC3H-1 muscle cells (S. K. Ambler and P. Taylor, J. Biol. Chem. 261:5866-5871, 1986) and muscarinic receptors in 1321N1 astrocytoma cells (S. B. Masters, T. K. Harden, and J. H. Brown, Mol. Pharmacol. 27:325-332, 1985) resulted in the rapid ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-09-01 00:00:00
abstract：:The current study was designed to investigate the importance of cationic amino acid transporters (CATs) for the L-arginine supply to nitric oxide (NO) synthases in mouse J774A.1 macrophages and human EA.hy926 endothelial cells. CAT-1 was expressed in both cell types, whereas CAT-2B was only expressed in activated macr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-01-01 00:00:00
abstract：:Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are members of the phospholipid growth factor family. A major limitation in the field to date has been a lack of receptor subtype-specific agonists and antagonists. Here, we report that dioctylglycerol pyrophosphate and dioctylphosphatidic acid are selectiv...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:The sulfoconjugation of tyrosyl residues is a widespread post-translational modification of biologically active proteins and peptides. The rat liver Golgi enzyme tyrosylprotein sulfotransferase has previously been shown to catalyze the transfer of a sulfate moiety from 5'-phosphoadenosine-3'-phosphosulfate to the synt...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:Our previous studies suggested that the dNTP/dNDP transporter systems that exist in mitochondria for transporting dNTP/dNDP from the cytoplasm to the mitochondria for mitochondrial DNA (mtDNA) synthesis play a critical role in delayed cytotoxicity of anti-human immunodeficiency virus (HIV) dideoxynucleoside analogs in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.007120
更新日期：2005-02-01 00:00:00
abstract：:Interleukin-2 (IL-2) is an immunoregulatory cytokine whose biological effects are mediated through interaction with specific receptors on the surface of target cells. Due to its presumed role in generating a normal immune response, IL-2 is being evaluated for the treatment of a variety of tumors, in addition to infect...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Electron affinities, approximated by lowest unoccupied molecular orbital (LUMO) energies, were determined for an extensive group of nitrated polycyclic aromatic hydrocarbons by ab initio methods at the STO-3G level. Significant correlations were demonstrated between nitroarene LUMO energy and the corresponding mutagen...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-06-01 00:00:00
abstract：:We studied the ability of norepinephrine to stimulate [3H]inositol trisphosphate production and calcium mobilization in rat-1 fibroblasts stably expressing the cloned alpha 1-adrenergic subtypes and their sensitivity to phorbol-12-myristate-13-acetate (PMA). It was observed that the three subtypes were able to activat...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:Several 2-amino-3-benzoylthiophenes were found to increase the binding of [3H]N6-cyclohexyladenosine to A1 adenosine receptors in rat brain membranes. Concentration-response curves were bell-shaped, with up to 45% stimulation of binding at 10 microM followed by inhibition at higher concentrations. Because these compou...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:Quinones undergo redox cycling and/or arylation reactions with key biomolecules involved with cellular Ca2+ regulation. The present study utilizes nanomolar quantities of the fluorogenic maleimide 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) to measure the reactivity of hyperreactive sulfhydryl moieti...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-05-01 00:00:00
