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)-NANM-binding sites is as follows: (d)-NANM = PCP-3-OH greater than (d)-cyclazocine greater than N-ethylphenylcyclohexylamine greater than PCP greater than (l)-cyclazocine = dextrorphan greater than (d/l)-ethylketocyclazocine greater than (d/l)-bremazocine greater than (1)-NANM greater than 1-phenylcyclohexylamine greater than levorphanol. Other opioid ligands, relatively selective for each of the types of opioid binding sites other than sigma, such as morphine (mu), H-Tyr-D-Ala(Me)Phe-NH-CH2-OH (mu), D-Ala2-D-Leu5-enkephalin (delta), tifluadom (kappa), and U 50488 (kappa) as well as etorphine and naloxone were all unable to compete with [3H](d)-NANM for specific binding even at a concentration of 1 microM. Regional distribution studies of [3H](d)-NANM-binding sites show high density in the hippocampus, thalamus, hypothalamus, and amygdala and low density in cerebellum and nonfrontal neocortex membranes of the rat brain. These binding sites are very sensitive to protein-modifying enzymes and reagents such as trypsin and N-ethylmaleimide and to heat denaturation. These results provide direct biochemical evidence for the existence of distinct (d)-NANM-binding sites in rat brain. In addition, this study supports the view that PCP and several of its analogues and the dextrorotatory isomers of psychotomimetic benzomorphans may act at a common recognition site in rat central nervous system.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Itzhak Y,Hiller JM,Simon EJsubject
Has Abstractpub_date
1985-01-01 00:00:00pages
46-52issue
1eissn
0026-895Xissn
1521-0111journal_volume
27pub_type
杂志文章abstract：:Previously, we showed that the human kappa-opioid receptor (hkor) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged U50,488H treatment. In the present study, we determined the mechanisms underlying this process. U50, 488H caused a significant down-regulation of the hkor, a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-10-01 00:00:00
abstract：:The present study demonstrates the following characteristic suramin actions on the purified skeletal muscle calcium release channel in single-channel current recordings and [(3)H]ryanodine binding to HSR: 1) Suramin (0.3-0.9 mM) induced a concentration-dependent increase in the open probability (P(o) congruent with 0....
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.3.543
更新日期：2001-03-01 00:00:00
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 num...
journal_title：Molecular pharmacology
pub_type： 评论,杂志文章,评审
doi：10.1124/mol.105.020727
更新日期：2006-02-01 00:00:00
abstract：:Ligands that selectively inhibit human α3β2 and α6β2 nicotinic acetylcholine receptor (nAChRs) and not the closely related α3β4 and α6β4 subtypes are lacking. Current α-conotoxins (α-Ctxs) that discriminate among these nAChR subtypes in rat fail to discriminate among the human receptor homologs. In this study, we desc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.100982
更新日期：2015-11-01 00:00:00
abstract：:Structural changes in the macromolecular targets of pharmacological agents can result in alterations in the efficacy of these agents. In previous studies, we identified a variant structural form of thymidylate synthase (TS) that is associated with relative resistance to 5-fluoro-2'-deoxyuridine, in a human colonic tum...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-08-01 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
abstract：:The aim of this study was to create and characterize constitutively active mutant (CAM) histamine H(1) receptors (H(1)R) using random mutagenesis methods to further investigate the activation process of the rhodopsin-like family of G protein-coupled receptors (GPCRs). This approach identified position 6.40 in TM 6 as ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.038547
更新日期：2008-01-01 00:00:00
abstract：:A quantum chemical study of adenosine, formycin, and their 2-NH2 and 2-F derivatives is performed. The tautomerism of neutral and protonated species as well as the protonation of adenosine, formycin, and their derivatives are theoretically studied using semiempirical MNDO and AM1, as well as ab initio STO-3G methods. ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:At sites of inflammation, endothelial cells play a major role in defining the types of leukocytes that are recruited to a specific area. This is accomplished, at least in part, through the cytokine induction of cell surface adhesion molecules, including vascular cell adhesion molecule 1 (VCAM-1). We investigated the r...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:In previous studies, it was shown that the overexpression of beta2-adrenoceptor (beta2AR) in the hearts of transgenic mice (Tg) leads to agonist-independent activation of adenylate cyclase and enhanced myocardial function. Here, we measured the physical coupling of beta2AR and Gs by evaluating the coimmunoprecipitatio...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.2.187
更新日期：1997-08-01 00:00:00
abstract：:MicroRNAs (miRNAs) have emerged as a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Over 700 miRNAs have been identified and sequenced in humans, and the number of miRNA genes is estimated at more than 1000. I...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.111.073528
更新日期：2011-10-01 00:00:00
abstract：:Cardiac function is regulated by many hormones and neurotransmitters that exert their physiological effects through the activation of G protein-coupled receptors (GPCRs). Identification of new GPCRs that might display a specific pattern of expression within the heart and differentially regulate specific cardiac functi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.054155
更新日期：2009-05-01 00:00:00
abstract：:The incorporation of leucine into protein was studied in Ca2+-depleted and Ca2+-restored preparations of normal liver cells isolated from fed, adult male rats. Ca2+-restored cells incorporated amino acid 5-10-fold more rapidly than did Ca2+-depleted cells for incubation periods up to 1 hr. Readdition of Ca2+ at suprap...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：:Cytosolic sulfotransferase (SULT)-mediated sulfation plays an essential role in the detoxification of bile acids and is necessary to avoid pathological conditions, such as cholestasis, liver damage, and colon cancer. In this study, using transgenic mice bearing conditional expression of the activated constitutive andr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.2.292
更新日期：2004-02-01 00:00:00
abstract：:Although the thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well established agents for the treatment of leukemia, controversies remain regarding their main mode of action. Previous evidence has suggested that although 6-TG exerts a cytotoxic effect through incorporation of 6-thioguanine nucleot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.1.102
更新日期：2002-07-01 00:00:00
abstract：:The retinoid (visual) cycle consists of a series of biochemical reactions needed to regenerate the visual chromophore 11-cis-retinal and sustain vision. Genetic or environmental factors affecting chromophore production can lead to blindness. Using animal models that mimic human retinal diseases, we previously demonstr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.117.111294
更新日期：2018-05-01 00:00:00
abstract：:Tumor cell resistance to anthracyclines and epipodophyllotoxins can be due to reduced drug accumulation and/or alterations in the activity of topoisomerase II (TOPO II). HL-60 cells selected in 0.05 micrograms/ml doxorubicin (DOX) are 10-fold and > 20-fold resistant to DOX and etoposide (VP-16), respectively. The accu...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:We reported earlier that delta 9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marihuana, increased markedly the level of unesterified arachidonic acid (AA) in guinea pig cerebral cortex slices prelabeled with [14C]AA. The purpose of the present study was to clarify the mechanism underlying THC-enhan...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:We identified a novel azaindole derivative, L-750,667, that has high affinity (Ki = 0.51 nM) and >2000-fold selectivity for D4 dopamine receptors compared with its activity at D2 and D3 dopamine receptors. L-750,667 had little affinity for rat D1/D5 dopamine receptors, sigma binding sites, or 5-hydroxytryptamine1A or ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:Thiourea, phenylthiourea, and methimazole perfused into rat liver stimulated the biliary efflux of GSSG without affecting the excretion of GSH into either the bile or the caval perfusate. The thiocarbamide moiety appears essential, since perfusion with urea, phenylurea, or N-methylimidazole did not stimulate GSSG rele...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
abstract：:To learn more about the binding conformation of phencyclidine (PCP) and to arrive at analogues of higher affinity, which may serve as noncompetitive N-methyl-D-aspartate receptor antagonists, eight optically pure PCP analogues were designed with the aid of computer. These compounds represent conformationally constrain...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:beta-arrestins have been shown to play important roles in regulation of signaling and desensitization of opioid receptors in many in vivo studies. The current study was carried out to measure the direct interaction of beta-arrestins with two functional intracellular domains, the third intracellular loop (I3L) and the ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.4.758
更新日期：2001-04-01 00:00:00
abstract：:The UGT1 locus is felt to be highly conserved between species, as is evident from the characterization of the locus in rodents and humans. In rabbits, cDNAs encoding proteins homologous to human UGT1A4, UGT1A6, and UGT1A7 have previously been identified. Here we demonstrate by Southern blot analysis, using exon 1 dive...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.1.89
更新日期：2000-07-01 00:00:00
abstract：:Neuronal cell lines provide a source of pure populations of neurons and allow the properties of many neurotransmitter receptors to be studied. However, none of these cells have been reported to express functional gamma-aminobutyric acid (GABA)A receptors. Indeed, there have been no reports of cell lines expressing fun...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-08-01 00:00:00
abstract：:Retina from 1-day-old chicks is a valuable tissue model for studying neuronal nicotinic receptors because it expresses a large number of the developmentally regulated high affinity [(3)H]epibatidine labeled nicotinic receptors. Most of these receptors contain the beta4 subunit associated with different alpha subunits....
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.6.1410
更新日期：2001-06-01 00:00:00
abstract：:Metallothioneins (MTs) are cytoplasmic proteins that sequester certain divalent cations and are considered a primary cellular defense against the toxic transition metal cadmium (Cd(2+)). MT-I/II(-/-) knockout [MT(-/-)] cells are available and serve as an excellent tool to study non-MT-related mechanisms in metal toler...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.014241
更新日期：2006-02-01 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
abstract：:The effect of breast cancer resistance protein (Bcrp/Abcg2) on the disposition of the phytoestrogens daidzein, genistein, and coumestrol was investigated using Bcrp(-/-) mice. Expression of the genes for either mouse Bcrp or human BCRP in MDCK II cells induced apically directed transport of the three phytoestrogens, w...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.034751
更新日期：2007-10-01 00:00:00
abstract：:Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathologic and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.120.119909
更新日期：2020-07-01 00:00:00
abstract：:The 90-kDa heat shock family (HSP90) of protein and two-component histidine kinases, although quite distinct at the primary amino acid sequence level, share a common structural ATP-binding domain known as the Bergerat fold. The Bergerat fold is important for the ATPase activity and associated chaperone function of HSP...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.2.289
更新日期：2002-08-01 00:00:00
