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 enzymatically dissociated adult rat superior cervical ganglion neurons. The cannabimimetic aminoalkylindole WIN 55,212-2 inhibited whole-cell Ca2+ currents in neurons injected 16-25 hr previously with rat brain CB1 cannabinoid receptor cRNA. Inhibition of the Ca2+ current was voltage and concentration dependent, with a maximal inhibition of 73% and an IC50 value of 47 nM. The synthetic cannabinoid analogue CP55,940 also inhibited Ca2+ currents, with a maximal inhibition of 38% and an IC50 value of 7 nM. Ca2+ current inhibition was blocked by inclusion of guanosine-5'-O-(2-thiodiphosphate) in the intracellular patch pipette solution or by pretreatment with pertussis toxin. Pretreatment with the N-type Ca2+ channel antagonist omega-conotoxin GVIA reduced the inhibition by 100 nM WIN 55,212-2 from 44% to 6%, indicating that N-type Ca2+ channels are a target of cannabinoid action. On washout of WIN 55,212-2, the Ca2+ current amplitude "overrecovered" in 47% of the neurons tested. Anandamide, the endogenous cannabimimetic compound, had an inconsistent effect on the voltage-dependent Ca2+ currents in the majority of neurons microinjected with cannabinoid receptor cRNA. Ca2+ channels were a specific effector target of the cannabinoid receptor, as two different K+ currents, the M current and the A current, were not modulated by the cannabimimetic WIN 55,212-2.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Pan X,Ikeda SR,Lewis DLsubject
Has Abstractpub_date
1996-04-01 00:00:00pages
707-14issue
4eissn
0026-895Xissn
1521-0111journal_volume
49pub_type
杂志文章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：:Recently we identified the serotonin reuptake inhibitor paroxetine as an inhibitor of G protein-coupled receptor kinase 2 (GRK2) that improves cardiac performance in live animals. Paroxetine exhibits up to 50-fold selectivity for GRK2 versus other GRKs. A better understanding of the molecular basis of this selectivity...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.089631
更新日期：2014-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:Metabolism of the pulmonary toxin, 4-ipomeanol, in microsomal preparations from rabbit liver and lung and in purified cytochrome P-450-dependent monooxygenase systems was investigated. The rate of formation of reactive electrophilic products from 4-ipomeanol was estimated by measuring covalent binding to protein or gl...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.60.6.1414
更新日期：2001-12-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.095554
更新日期：2015-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.043505
更新日期：2008-04-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.014225
更新日期：2005-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.052548
更新日期：2009-03-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:The heart is richly endowed with K(ATP) channels, which function as biological sensors, regulating membrane potentials and electrical excitability in response to metabolic alterations. We recently reported that the cytochrome P450 metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), potently activate car...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.5.1076
更新日期：2002-11-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:The congenital long QT syndrome is an inherited disorder characterized by a delay in cardiac repolarization, leading to lethal cardiac arrhythmias such as torsade de pointes. One form of this disease involves mutations in the voltage-dependent cardiac Na(+) channel, which includes an in-frame deletion of three amino a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：:Guinea pig lung microsomes converted arachidonic acid (AA) to two classes of cytochrome P450 (P450)-dependent metabolites, 16- through 20-hydroxyeicosatetraenoic acids [(16-20)-OH-AA] and epoxyeicosatrienoic acids (EETs). The rate of formation of (16-20)-OH-AA was approximately 3-fold higher in microsomes from beta-na...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:Chronic stimulation of beta-adrenoceptors leads to increased mRNA and protein levels of pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in the heart. In the present study the time course is reported of the effect of isoprenaline infusions on myocardial mRNA levels of Gi alpha-2, Gi alp...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:Valproic acid (VPA) is a widely used antiepileptic agent that is undergoing clinical evaluation for anticancer therapy. We assessed the effects of VPA on angiogenesis in vitro and in vivo. In human umbilical vein endothelial cells, therapeutically relevant concentrations of VPA (0.25 to 1 mM) inhibited proliferation, ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.3.520
更新日期：2004-03-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.080879
更新日期：2013-02-01 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：: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 effect of halothane on synthesis of retained and secreted proteins was investigated using isolated perfused rat livers. Anesthetic exposure rapidly inhibited synthesis of total liver proteins in a dose-dependent manner by a mechanism which appeared to involve reduced rates of both peptide chain initiation and elon...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:This study assessed how conformational information encoded by ligand binding to δ-opioid receptors (DORs) is transmitted to Kir3.1/Kir3.2 channels. Human embryonic kidney 293 cells were transfected with bioluminescence resonance energy transfer (BRET) donor/acceptor pairs that allowed us to evaluate independently reci...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.081950
更新日期：2013-02-01 00:00:00
abstract：:It is widely accepted that cAMP signaling is compartmentalized within cells. However, our knowledge of how receptors, cAMP signaling enzymes, effectors, and other key proteins form specific signaling complexes to regulate specific cell responses is limited. The multicomponent nature of these systems and the spatiotemp...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.117.110825
更新日期：2018-04-01 00:00:00
abstract：:The sympathetic nervous system modulates cardiac contractility and rate by activating beta-adrenergic receptors (beta AR) expressed on cardiac myocytes and specialized cells in the sinoatrial node and the conduction system. Recent clinical studies have suggested that beta-adrenergic receptors also play a role in cardi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-09-01 00:00:00
abstract：:The X-ray structure of the bacterial sodium channel NavAb provides a new template for the study of sodium and calcium channels. Unlike potassium channels, NavAb contains P2 helices in the outer-pore region. Because the sequence similarity between eukaryotic and prokaryotic sodium channels in this region is poor, the s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.078212
更新日期：2012-07-01 00:00:00
abstract：:Previously, we reported the presence of dual promoters, referred to as distal (DP) and proximal, with a negative regulatory element between them in the mouse mu-opioid receptor (mor) gene. Here we have identified a positive regulatory element influencing mor DP transcription, which contains multiple consensus binding ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.6.1486
更新日期：2001-06-01 00:00:00
abstract：:Aspartyl aminopeptidase (DNPEP) has been implicated in the control of angiotensin signaling and endosome trafficking, but its precise biologic roles remain incompletely defined. We performed a high-throughput screen of ∼25,000 small molecules to identify inhibitors of DNPEP for use as tools to study its biologic funct...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.093070
更新日期：2014-08-01 00:00:00
