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. Using a sequential immunodepletion procedure with anti-alpha6, anti-beta3, anti-beta2, and anti-beta4 antibodies, we purified an alpha4beta4 nicotinic receptor subtype that accounts for approximately 20 to 25% of the high affinity [(3)H]epibatidine labeled receptors present in retina at that developmental time. Immunoprecipitation and Western blotting experiments confirmed that the purified subtype contains only the alpha4 and beta4 subunits. This receptor binds a number of agonists and the antagonist dihydro-beta-erythroidine with nanomolar affinity, whereas it has micromolar affinity for the alpha-conotoxin MII and methyllycaconitine toxins and other nicotinic antagonists. Comparison of the pharmacological profile of this purified native subtype with that of the same subtype transiently expressed in human BOSC23 cells showed that they have very similar rank orders and absolute Ki values for several nicotinic drugs. Finally, because chick retina expresses an alpha6beta4-containing subtype with a high affinity for the alpha-conotoxin MII, we used native and transfected alpha4beta4 and alpha6beta4 subtypes to investigate the relative contributions of the alpha and beta subunits to this binding, and found that the alpha6 subunit determines the high affinity for this toxin.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Barabino B,Vailati S,Moretti M,McIntosh JM,Longhi R,Clementi F,Gotti Cdoi
10.1124/mol.59.6.1410keywords:
subject
Has Abstractpub_date
2001-06-01 00:00:00pages
1410-7issue
6eissn
0026-895Xissn
1521-0111journal_volume
59pub_type
杂志文章abstract：:As noted previously, in N1E-115 neuroblastoma cells, carbamylcholine, a muscarinic cholinergic agonist, increased cGMP over 15-fold and decreased basal and prostaglandin E1 (PGE1)-stimulated cAMP content. In contrast to the stimulatory effects of PGE1 on cAMP, which were immediate, the carbamylcholine-induced decrease...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-08-01 00:00:00
abstract：:Beta-adrenergic receptors were characterized in a particulate fraction of human auricles obtained from patients operated upon for coronary insufficiency or valvular disease. [125I] Hydroxybenzylpindolol binding was evaluated in terms of kinetics; KD and Bmax values; and inhibition of binding in the presence of 10 micr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:The 2,3,7,8-tetrachlorodibenzo-p-dioxin-transformed aryl hydrocarbon receptor (AHR) complex binds to xenobiotic-responsive element (XRE) sequences in the 5' flanking region of the CYP1A1 gene, resulting in initiation of transcription. Both components of the transformed AHR complex [the ligand-binding AHR monomer and t...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacolo...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.115.098509
更新日期：2015-10-01 00:00:00
abstract：:Caveolins have been recognized over the past few decades as key regulators of cell physiology. They are ubiquitously expressed and regulate a number of processes that ultimately impact efficiency of cellular processes. Though not critical to life, they are central to stress adaptation in a number of organs. The follow...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.117.111237
更新日期：2018-04-01 00:00:00
abstract：:A substantial body of research implicates L-cysteine sulfinic acid (L-CSA) as a neurotransmitter. However, all physiological actions of L-CSA that have been pharmacologically characterized are mediated by cross-activation of glutamate receptors, and no receptor has been identified that is primarily activated by L-CSA....
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:Lack of high potency agonists has restricted analysis of the G protein-coupled receptor GPR35. Moreover, marked variation in potency and/or affinity of current ligands between human and rodent orthologs of GPR35 has limited their productive use in rodent models of physiology. Based on the reported modest potency of th...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.089482
更新日期：2014-01-01 00:00:00
abstract：:The beta 3-adrenergic receptor (beta 3AR) is a member of the super-family of G protein-coupled receptors that are characterized by seven putative transmembrane helices connected by hydrophilic loops. The mechanism by which the activated beta ARs transmit the signals across the plasma membrane involves the stimulation ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a cyclopentenonic prostaglandin endowed with powerful anti-inflammatory activities, as shown in animal models of inflammatory/autoimmune diseases, where pharmacological administration of this prostanoid can ameliorate inflammation and local tissue damage via act...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.038042
更新日期：2007-11-01 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：:A series of aminotriarylmethane dyes were examined for binding to the nicotinic acetylcholine receptor (AChR) from Torpedo californica. Several compounds were found to bind to the noncompetitive antagonist site of the AChR as demonstrated by inhibition of [3H]phencyclidine binding; apparent KD values ranged from 50 nM...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.55.1.159
更新日期：1999-01-01 00:00:00
abstract：:UDP-glucuronosyltransferase (UGT) 1A1 glucuronidates endogenous metabolites, such as bilirubin, and exogenous substances, and plays a critical role in their detoxification and excretion. In a previous article, we described the phenobarbital response activity to a 290-base pair (bp) distal enhancer sequence (-3499/-321...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.007161
更新日期：2005-03-01 00:00:00
abstract：:The μ-opioid receptor gene undergoes extensive alternative splicing to generate an array of splice variants. One group of splice variants excludes the first transmembrane (TM) domain and contains six TM domains. These 6TM variants are essential for the action of a novel class of analgesic drugs, including 3-iodobenzoy...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.120.119453
更新日期：2020-10-01 00:00:00
abstract：:In an effort to combine the benefits of fibrinolytics, such as staphylokinase, with those of thrombin inhibitors for the prevention of vessel reocclusion after vascular injury, we have produced several chimeric proteins with plasminogen-activating and thrombin-inhibiting properties. Fusion proteins were constructed co...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.2.203
更新日期：2002-08-01 00:00:00
abstract：:Multiple lines of evidence indicate that the platinum-containing cancer drugs enter cells, are distributed to various subcellular compartments, and are exported from cells via transporters that evolved to manage copper homeostasis. The cytotoxicity of the platinum drugs is directly related to how much drug enters the ...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.109.063172
更新日期：2010-06-01 00:00:00
abstract：:The subunit composition and pharmacological regulation of rat neuronal nicotinic cholinergic receptors were assessed. Specific immunoprecipitation was determined in solubilized rat brain homogenates using [3H]cytisine, a high affinity agonist at nicotinic receptors, in conjunction with polyclonal antisera generated ag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modes...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.119.117143
更新日期：2019-10-01 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：: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 exchange of tritium into water from saxitoxin molecules that were radiolabeled at the C-11 methylene position was measured at 37 degrees in solution and in suspensions of brain membranes. High concentrations of membrane receptors were used to assure that more than 80% of the total saxitoxin (STX) present was speci...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-03-01 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：:The anti-human immunodeficiency virus (-HIV) nucleoside analogs azidothymidine (AZT), dideoxycytidine (ddC), dideoxyinosine (ddl), dideoxydidehydrothymidine (D4T), and dideoxydidehydrocytidine (D4C) and the anticancer drug cytosine arabinoside (AraC) were compared for their effects on the mitochondrial DNA (mtDNA) con...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:The aryl hydrocarbon receptor (AHR) and its DNA binding partner, the AHR nuclear translocator (ARNT), are basic helix-loop-helix transcription factors that mediate many of the toxic and carcinogenic effects of polyhalogenated aromatic hydrocarbons. The basic regions of the AHR and ARNT contact the GCGTG recognition si...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:2-Hydroxy-4(-2,2,3,3,3-pentafluoropropoxy)-benzoic acid (UR-1505), a new molecule chemically related to salicylic acid, has immunomodulator properties and is currently under clinical development for treatment of atopic dermatitis. The present work describes the immunomodulatory profile of UR-1505. UR-1505 targets T ce...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.035212
更新日期：2007-08-01 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：:5-Hydroxytryptamine3 (5-HT3) receptors are ligand-gated ion channels that mediate neurotransmission by serotonin in the central nervous system. Pharmacological inhibition of 5-HT3 receptor activity has therapeutic potential in several psychiatric diseases, including depression and anxiety. The recently approved multim...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.118.113530
更新日期：2018-12-01 00:00:00
abstract：:TNP-ATP has become widely recognized as a potent and selective P2X receptor antagonist, and is currently being used to discriminate between subtypes of P2X receptors in a variety of tissues. We have investigated the ability of TNP-ATP to inhibit alpha,beta-methylene ATP (alpha,beta-meATP)-evoked responses in 1321N1 hu...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.6.1502
更新日期：2000-12-01 00:00:00
abstract：:Inflammation contributes to pain hypersensitivity through multiple mechanisms. Among the most well characterized of these is the sensitization of primary nociceptive neurons by arachidonic acid metabolites such as prostaglandins through G protein-coupled receptors. However, in light of the recent discovery that the no...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.040832
更新日期：2008-02-01 00:00:00
abstract：:Binding by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the Ah receptor leads to transcriptional activation of several genes and a toxicity syndrome that includes tumor promotion, wasting, hormonal and immune system dysfunction, and death. Recent findings indicate that TCDD may also affect cardiac function. Here, we ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：:We tested several histamine H(1) receptor (H(1)R) and antagonists for their differences in agonists binding affinities between human and guinea pig H(1)Rs transiently expressed in African green monkey kidney (COS-7) cells. Especially, the bivalent agonist histaprodifen-histamine dimer (HP-HA) shows a higher affinity f...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.008847
更新日期：2005-04-01 00:00:00
