Abstract：
:Aflatrem, a mycotoxin from Aspergillus flavus, potentiates the gamma-aminobutyric acid (GABA)-induced chloride current. This positive allosteric regulatory action of aflatrem was quantitatively studied on the GABAA receptor channel expressed in Xenopus oocytes after injection with chick brain mRNA under voltage-clamp conditions. In this model system, aflatrem potentiates the current induced by 5 microM GABA in a concentration-dependent manner. Half-maximal potentiation was obtained with 2.4 microM aflatrem and maximal stimulation of the GABA (5 microM) response was more than 10-fold. The potentiation was not associated with a change of the reversal potential of the GABA-induced current. In the presence of 2 microM aflatrem, the GABA dose-response curve shifted to lower concentrations, with the Ka decreasing from 28 to 7 microM and the Hill coefficient, n, from 1.5 to 0.8, as measured at a membrane potential of -100 mV. At saturating concentration of GABA (250 microM), aflatrem (10 microM) was still able to enhance the current by about 21%. Further experiments suggest that the site of action of aflatrem on the GABAA receptor channel complex is different from that of benzodiazepines, pentobarbital, and picrotoxin. Aflatrem (10 microM) had no significant effect on the coexpressed voltage-dependent sodium and calcium channels and on the kainate channel. The potentiating action of aflatrem on the GABAA receptor channel may explain the initial symptoms of intoxication caused by aflatrem in vivo, i.e., diminished activity or immobility of the affected animal.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Yao Y,Peter AB,Baur R,Sigel Esubject
Has Abstractpub_date
1989-03-01 00:00:00pages
319-23issue
3eissn
0026-895Xissn
1521-0111journal_volume
35pub_type
杂志文章abstract：:Previous studies showed that lapatinib and obatoclax interact in a greater-than-additive fashion to cause cell death and do so through a toxic form of autophagy. The present studies sought to extend our analyses. Lapatinib and obatoclax killed multiple tumor cell types, and cells lacking phosphatase and tensin homolog...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.081539
更新日期：2012-12-01 00:00:00
abstract：:Glutathione-liganded binuclear dinitrosyl iron complex (glut-BDNIC) has been proposed to be a donor of nitric oxide (NO). This study was undertaken to investigate the mechanisms of vasoactivity, systemic hemodynamic effects, and pharmacokinetics of glut-BDNIC. To test the hypothesis that glut-BDNICs vasodilate by rele...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.117.110957
更新日期：2018-05-01 00:00:00
abstract：:The possibility that vasoactive intestinal polypeptide (VIP) may facilitate the nicotine-mediated induction of adrenal medullary tyrosine hydroxylase (TH) was investigated with primary cultures (5-7 days in vitro) of bovine adrenal chromaffin (BAC) cells. Exposure of BAC cells to 100 microM nicotine led to only a marg...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:Binding of [3H](d)-N-allylnormetazocine ([3H](d)-NANM) to rat brain membranes is stereospecific, reversible, and saturable (Bmax = 260 fmol/mg of protein) and manifests moderately high affinity (Kd = 20 nM). The rank order of potency among opioidbenzomorphans and phencyclidine (PCP) analogs for competition for [3H](d)...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Previous studies have demonstrated that the quinone group may play an important role in modulating the alkylating activity of quinone alkylating agents. Introduction of a quinone moiety markedly increased the alkylating activity and cytotoxic activity of the model quinone alkylating agents benzoquinone mustard and ben...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:The precise mechanism by which the broad-spectrum anti-RNA virus agent ribavirin elicits its in vitro antiviral effect has remained a matter of debate. We have demonstrated that inhibition of cellular inosine monophosphate dehydrogenase (IMPDH) activity, and thus depletion of intracellular GTP pools, is the predominan...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.020057
更新日期：2006-04-01 00:00:00
abstract：:A site-directed alkylating agent was used to inactivate one or more types of opioid receptor in two bioassay preparations in the presence of type-selective ligands as protectors of other opioid receptor types. Since the pharmacological potency of an agonist is decreased when the receptor type through which it acts has...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:We have recently demonstrated that the alpha 2-adrenergic radioligand [3H]idazoxan also labels additional sites that do not recognize catecholamines but bind with high affinity several chemically distinct drugs previously assumed to be highly selective for alpha 2-adrenergic receptors [Mol. Pharmacol. 35:324-330 (1989...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:Kinetics of the interactions between the neuromuscular blocker alcuronium, the specific muscarinic antagonist N-[methyl-3H] methyl scopolamine ([3H]NMS), and muscarinic receptors were investigated in homogenates of rat heart atria. Two effects of alcuronium on the binding of [3H]NMS could be distinguished. (a) Alcuron...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-04-01 00:00:00
abstract：:15-Deoxy delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), an activator of peroxisome proliferator-activated receptor (PPAR)-gamma and -delta, is a prostanoid metabolite with anti-inflammatory actions. In intrauterine tissues, proinflammatory cytokines and prostaglandins have been identified as playing key roles in the ma...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.009449
更新日期：2005-07-01 00:00:00
abstract：:Bioassay-guided fractionation was used to isolate the lignan polygamain as the microtubule-active constituent in the crude extract of the Mountain torchwood, Amyris madrensis. Similar to the effects of the crude plant extract, polygamain caused dose-dependent loss of cellular microtubules and the formation of aberrant...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.075838
更新日期：2012-03-01 00:00:00
abstract：:The dissociation constants (Kd values) of substance P (SP), physalaemin, kassinin, and SP analogues acting on SP receptors in guinea pig ileal longitudinal muscle strips were determined by the pharmacological procedures of Furchgott [Adv. Drug Res. 3:21-55 (1966)]. This method involves analysis of the concentration-re...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:A Walker 256 rat carcinoma cell line (WR) has been shown to be resistant to a broad spectrum of bifunctional nitrogen mustards (NM) in cell culture. The parent cell line (WS) from which the WR cells were selected retains marked sensitivity to this class of drugs. Karyotype analysis showed that the parent WS had a chro...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：:Signaling by the insulin-like growth factor (IGF)-1 receptor (IGF-1R) has been implicated in the promotion and aggressiveness of breast, prostate, colorectal, and lung cancers. The IGF binding proteins (IGFBPs) represent a class of natural IGF antagonists that bind to and sequester IGF-1/2 from the IGF-1R, making them...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.016998
更新日期：2006-03-01 00:00:00
abstract：:The aliphatic adenine analogues, D-eritadenine, L-eritadenine, L-threoeritadenine, and 9-(S)-(2,3-dihydroxypropyl)adenine [(S)DHPA] function as inhibitors/inactivators of purified S-adenosylhomocysteine (AdoHcy) hydrolase, but these compounds did not induce reduction of enzyme-bound NAD+. D-Eritadenine, L-eritadenine,...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:Metabotropic glutamate receptor 5 (mGlu5) is a target for the treatment of central nervous system (CNS) disorders, such as schizophrenia and Alzheimer's disease. Furthermore, mGlu5 has been shown to play an important role in hippocampal synaptic plasticity, specifically in long-term depression (LTD) and long-term pote...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.082891
更新日期：2013-04-01 00:00:00
abstract：:Extracellular protons inhibit N-methyl-D-aspartate (NMDA) receptors with an IC50 value in the physiological pH range. To identify the molecular determinants of proton sensitivity, we used scanning mutagenesis of the NR1 subunit to search for residues that control proton inhibition of NMDA receptors. Homology modeling ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.6.1212
更新日期：2003-06-01 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：: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：:Secreted R-spondin proteins (RSPOs1-4) function as adult stem cell growth factors by potentiating Wnt signaling. Simultaneous binding of distinct regions of the RSPO Fu1-Fu2 domain module to the extracellular domains (ECDs) of the LGR4 G protein-coupled receptor and the ZNRF3 transmembrane E3 ubiquitin ligase regulate...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.095133
更新日期：2015-01-01 00:00:00
abstract：:Low-density lipoprotein (LDL) is known to be a mitogenic factor for vascular smooth muscle cells (VSMCs), fibroblasts, and endothelial cells. In the current study, we describe possible intracellular mechanisms by which LDL elicits its mitogenic effects. Stimulation of VSMCs with LDL resulted in a pertussis-toxin (PTX)...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.3.389
更新日期：1997-09-01 00:00:00
abstract：:Fusion proteins between the human 5-hydroxytryptamine (5-HT)(1A) receptor and either wild type or certain pertussis toxin-resistant forms of G(o1)alpha and G(i1)alpha display constitutive GTPase activity that can be inhibited by the inverse agonist spiperone. Addition of recombinant regulator of G protein signaling (R...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.5.1211
更新日期：2002-05-01 00:00:00
abstract：:The cDNAs for the four murine aryl hydrocarbon (Ah) receptor alleles were cloned and sequenced, and the deduced amino acid sequences were compared. The Ahb-1 allele encodes a protein of 805 amino acids, the Ahd and Ahb-2 alleles encode proteins of 848 amino acids, and the Ahb-3 allele encodes a protein of 883 amino ac...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Guanine nucleotide-binding proteins (G proteins) transduce signals from agonist- and light-sensitive receptors. In the visual excitation system, the photon receptor rhodopsin is coupled to the G protein Gt (transducin). Gt is composed of alpha, beta, and gamma subunits; the alpha subunit binds guanine nucleotide, wher...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:A family of five cholinergic muscarinic receptor genes (m1, m2, m3, m4, and m5) has recently been identified and cloned. In order to investigate the pharmacological properties of the individual muscarinic receptors, we have transfected each of these genes into Chinese hamster ovary cells (CHO-K1) and have established ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Regulator of G protein signaling (RGS) proteins accelerate the endogenous GTPase activity of Galpha(i/o) proteins to increase the rate of deactivation of active Galpha-GTP and Gbetagamma signaling molecules. Previous studies have suggested that RGS proteins are more effective on less efficiently coupled systems such a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.043547
更新日期：2008-05-01 00:00:00
abstract：:Neuroactive steroids have been postulated to cause anesthesia by binding to unique steroid recognition sites on gamma-aminobutyric acid (GABA) receptors and modulating GABA receptor function. Steroids interact with these sites diastereoselectively, but it is unknown whether steroid sites show enantioselectivity. To ad...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:We have investigated the effect of chronic flurazepam HCl treatment on the gamma-aminobutyric acid (GABA)A receptor complex in cultured mammalian cortical neurons. Chronic flurazepam (1-5 microM, for 1-10 days) treatment did not produce any changes in the morphological appearance or the cell protein content of cortica...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-04-01 00:00:00
abstract：:2',3'-Dideoxyadenosine (ddAdo) and its deamination product 2',3'-dideoxyinosine (ddIno) (didanosine) inhibit the replication and infectivity of the human immunodeficiency virus (HIV) in a number of in vitro assay systems. Early clinical studies (phase I) have indicated a role for ddIno in the treatment of patients wit...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-07-01 00:00:00
abstract：:Neuromedin U (NmU) is a 25 amino acid peptide prominently expressed in the upper gastrointestinal (GI) tract and central nervous system. It is highly conserved throughout evolution and induces smooth muscle contraction in a variety of species. Our understanding of NmU biology has been limited because the identity of i...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.4.870
更新日期：2000-10-01 00:00:00
