Abstract:
:Chick brain mRNA was isolated and injected into Xenopus oocytes. This led to the expression of gamma-aminobutyrate (GABA) channels easily accessible for current measurements using the voltage clamp technique. The effect of the anthelmintic natural product avermectin B1a on the GABA current was studied quantitatively. In the presence of the drug, GABA-induced chloride currents were strongly enhanced in a dose-dependent manner. Half-maximal stimulation of the current evoked by 5 microM GABA was found with about 0.1 microM avermectin B1a. Avermectin B1a did not affect the reversal potential of the current or the maximal response elicited by GABA, and did not alter the membrane permeability in the absence of GABA. The major effects of avermectin B1a were a shift of the Ka for GABA from 21 microM to 2 microM, and a decrease of the apparent Hill coefficient for GABA from 1.7 to 1.1. Furthermore, in the presence of avermectin B1a, desensitization of the GABA current was strongly inhibited. The benzodiazepine-binding site ligand Ro 15-1788 did not affect the action of avermectin B1a if present at concentrations up to 1 microM. The stimulatory effects of the drug were additive to the ones by the barbiturate pentobarbital, if both agents were added at low concentrations. At higher concentrations each of these agents inhibited the stimulatory effects of the other.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Sigel E,Baur Rsubject
Has Abstractpub_date
1987-12-01 00:00:00pages
749-52issue
6eissn
0026-895Xissn
1521-0111journal_volume
32pub_type
杂志文章abstract::We compared the binding of [N-methyl-3H]scopolamine methyl chloride [( 3H]NMS) and pirenzepine to muscarinic receptors in four regions of the rat central nervous system (cortex, hippocampus, striatum, and cerebellum) and in rat heart. Equilibrium binding studies suggested the existence of three classes of receptors: A...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
abstract::The rat mu-opioid receptor clone in which novel exon 5 was found in the place of exon 4 (MOR-1B) was one of the first MOR-1 variants described. We now have identified the mouse homolog of the rat MOR-1B as well as four additional variants derived from splicing from exon 3 into different sites within exon 5. The sequen...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.011858
更新日期:2005-09-01 00:00:00
abstract::The effect of ethanol on intracellular ionized calcium concentrations (Cai) was studied in synaptosomes isolated from mouse whole brain and in hepatocytes isolated from rat liver. The fluorescent calcium chelator, fura-2, was used to quantitate Cai. Incubation of synaptosomes with ethanol (350-700 mM) increased restin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Differential display reverse transcription-polymerase chain reaction was used to identify mRNAs that are differentially expressed in the brain of rats treated chronically with the reference tricyclic antidepressant, imipramine, in comparison with control rats. The gene encoding for a mutation suppressor for Sec4-8 yea...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.62.6.1332
更新日期:2002-12-01 00:00:00
abstract::Amitriptyline is a classic tricyclic antidepressant (TCA) and has been used to treat the depression and anxiety of patients with cancer, but its relevance to cancer cell apoptosis is not known. In the present study, we demonstrated that amitriptyline inhibited cyclin D2 transactivation and displayed potential antimyel...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.068122
更新日期:2011-04-01 00:00:00
abstract::We have previously reported that, depending on the dose, nitric oxide (NO)-generating agents exert a dual facilitatory and inhibitory action on glutamatergic transmission on the rostral ventrolateral medulla (RVLM) neurons. The molecular mechanisms underlying the NO-mediated synaptic inhibition have not yet been defin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.000554
更新日期:2004-09-01 00:00:00
abstract::The endogenous bronchodilator, S-nitrosoglutathione (GSNO), increases expression, maturation, and function of both the wild-type and the DeltaF508 mutant of the cystic fibrosis transmembrane conductance regulatory protein (CFTR). Though transcriptional mechanisms of action have been identified, GSNO seems also to have...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.023242
更新日期:2006-10-01 00:00:00
abstract::The present study was conducted to establish a pharmacological method of controlling growth of vascular smooth muscle cells (VSMC) by blocking calcium entry. In cultured rat VSMC, 1 nM platelet-derived growth factor (PDGF) induced a biphasic elevation of cytoplasmic free calcium concentration, ([Ca2+]c). The second su...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Healing of gastrointestinal mucosal lesions occurs through two processes: an early one involving cell migration and a later one in which cell division replaces lost cells. Both processes require the presence of polyamines, but the mechanism of action of these compounds is unknown. In the present study, we examined the...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::Mitsuya and Broder [Proc. Natl. Acad. Sci. USA 83:1911-1915 (1986)] demonstrated that every purine (adenosine, guanosine, and inosine) and pyrimidine (cytidine and thymidine) nucleoside containing the 2',3'-dideoxyribose configuration, when evaluated against human immunodeficiency virus (HIV) in vitro, significantly s...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Previous studies have established that two Xbal polymorphic restriction fragments [11.5 and 44 kilobases (kb)] hydridizing to a full length debrisoquin hydroxylase cDNA are associated with two different mutant alleles for the debrisoquin hydroxylase gene (IID6). An independent allele, defined by Xbal 16- and 9-kb frag...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::We describe the structural and functional features of the human alpha3 nicotinic receptor subunit promoter. A 0.35-kb region immediately upstream of the start codon was identified that when transfected in human neuroblastoma cells was able to drive the expression of the luciferase reporter gene with a strength compara...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.51.2.250
更新日期:1997-02-01 00:00:00
abstract::The two forms of pituitary adenylate cyclase-activating polypeptide, PACAP27 and PACAP38, are two neuropeptide hormones related to the vasoactive intestinal peptide/secretin/ glucagon family of peptides. PACAP receptors that are positively coupled to adenylyl cyclase and phospholipase C have been identified in culture...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::We studied the mechanism by which the peptide omega-grammotoxin-SIA inhibits voltage-dependent calcium channels. Grammotoxin at concentrations of > 50 nM completely inhibited inward current carried by 2 mM barium through P-type channels in rat cerebellar Purkinje neurons when current was elicited by depolarizations up...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.52.6.1095
更新日期:1997-12-01 00:00:00
abstract::Modulation of neuronal ion channels by the cloned rat brain CB1 cannabinoid receptor was investigated with the use of a heterologous neuronal expression system. Transient expression of the rat brain CB1 cannabinoid receptor was accomplished through microinjection of in vitro transcribed cRNA into the cytoplasm of enzy...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::1-Deoxynojirimycin (DNM) is a saccharide decoy that inhibits cellular alpha-glucosidase I-II activity. Treatment by DNM of human immunodeficiency virus (HIV)-infected lymphocyte cultures inhibits virus spread. The functional properties of the membrane-associated Env glycoprotein (Env) modified in the presence of DNM r...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.61.1.186
更新日期:2002-01-01 00:00:00
abstract::Activation of endothelial nitric-oxide synthase (eNOS) has been shown to occur through various pathways involving increases in the cytosolic Ca(2+) concentration, activation of the phosphatidylinositol-3' kinase/Akt pathway, as well as regulation by other kinases and by protein-protein interactions. We have recently r...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.63.4.886
更新日期:2003-04-01 00:00:00
abstract::Cytosolic sulfotransferase 1C3 (SULT1C3) is the least characterized of the three human SULT1C subfamily members. Originally identified as an orphan SULT by computational analysis of the human genome, we recently reported that SULT1C3 is expressed in human intestine and LS180 colorectal adenocarcinoma cells and is upre...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.106005
更新日期:2016-11-01 00:00:00
abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), beta-naphthoflavone (beta NF), and phenobarbital (PB) cause marked induction of cytochrome P-450 (P-450)-mediated arachidonic acid metabolism in chick embryo liver. We show here that the P-450 arachidonic acid epoxygenases induced by TCDD and beta NF are immunochemically ind...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::EM-652 (SCH 57068) is a new orally active antiestrogen that demonstrates pure antagonistic effects in the mammary gland and endometrium. In vivo studies have shown that EM-652 is primarily glucuronidated at the 7-hydroxy position in rats and that the metabolite is present in the plasma of female monkeys and human subj...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.3.636
更新日期:2001-03-01 00:00:00
abstract::The interaction of quinidine with a cloned human cardiac potassium channel (HK2) expressed in a stable mouse L cell line was studied using the whole-cell tight-seal voltage-clamp technique. Quinidine (20 microM) did not affect the initial sigmoidal activation time course of the current. However, it reduced the peak cu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00
abstract::Up-regulation of fractalkine is involved in vascular and tissue damage in inflammatory conditions. Resveratrol has been shown to have anti-inflammatory, antioxidant, and antitumor activities. Its regulatory effects on expression of fractalkine in vascular endothelial cells and fractalkine receptor CX3CR1 in monocytes ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.022392
更新日期:2006-07-01 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
abstract::Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) are ubiquitously expressed in the mammalian central nervous system, where they exert trophic actions on both neuronal and glial cells. However, the acute actions of PDGF on synaptic transmission are unknown. We report a novel regulatory action of PDGF/P...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Molecular cloning of membrane-spanning mammalian adenylyl cyclases (ACs) has led to the discovery of nine different isotypes, making ACs potentially useful therapeutic targets. This study investigated the mechanism by which fungicidal nitroimidazole compounds modulate AC activity. Current evidence indicates that biolo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.63.3.624
更新日期:2003-03-01 00:00:00
abstract::Dilute formalin injected into the rat hindpaw as a nociceptive stimulus increases neurokinin-1 receptor (NK-1R) mRNA levels in the dorsal horn of the spinal cord. Increased NK-1R mRNA levels could result from increased mRNA stability or an increased rate of NK-1R mRNA transcription. In this study, RNA samples prepared...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::The purpose of these studies was to support the hypothesis that an undiscovered cannabinoid receptor exists in brain. [(35)S]GTP gamma S binding was stimulated by anandamide and WIN55212-2 in brain membranes from both CB(1)(+/+) and CB(1)(-/-) mice. In contrast, a wide variety of other compounds that are known to acti...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract::Schizophrenia (SZ), schizoaffective (SZA), and bipolar (BP) disorder are neurodevelopmental psychopathological conditions related, in part, to genetic load and, in part, to environmentally induced epigenetic dysregulation of chromatin structure and function in neocortical GABAergic, glutamatergic, and monoaminergic ne...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113415
更新日期:2019-01-01 00:00:00
abstract::The mechanism underlying the crosstalk between multiple G protein-coupled receptors remains poorly understood. We previously reported that prostaglandin E receptor EP1 facilitates dopamine D1 receptor signaling in striatal slices and promotes behavioral responses induced by D1 receptor agonists. Here, using human embr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.087288
更新日期:2013-09-01 00:00:00
abstract::The binding of [3H]quinuclidinyl benzilate ([3H]QNB) to cardiac muscarinic receptors was inhibited not only by classical muscarinic antagonists but also by nicotinic blocking agents and inhibitors of acetylcholinesterase. Gallamine, pancuronium, ambenonium, and decamethonium were the most potent of these agents examin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-07-01 00:00:00