Abstract：
:Ca-dependent, K-stimulated 86Rb efflux, a measure of Ca-activated K conductance in rat brain synaptosomes, was blocked by phenothiazines and haloperidol. Micromolar concentrations of the phenothiazines, fluphenazine and trifluoperazine, and haloperidol, a non-phenothiazine antipsychotic and calmodulin antagonist, selectively inhibited the Ca-activated K channels. The IC50 values of all three agents for inhibition of the Ca-activated K channels was on the order of 0.5-1 microM. Measurements of K-stimulated 45Ca uptake indicated that the effects of these agents on Ca-activated K channels was not due to inhibition of Ca influx through voltage-gated Ca channels. Sulpiride, a potent antipsychotic with weak anti-calmodulin activity, was a relatively weak inhibitor of Ca-activated K channels. Calmidazolium (compound R-24571) and W7, two non-phenothiazine calmodulin antagonists, did not selectively inhibit Ca-activated K channels. Biphasic dose response curves for inhibition of the Ca-dependent, K-stimulated 86Rb efflux by the phenothiazines raise the possibility that there may be two kinds of Ca-activated K channels in rat brain presynaptic terminals, with different sensitivities to the phenothiazines. These results demonstrate that two phenothiazines and haloperidol are potent and relatively selective inhibitors of Ca-activated K channels in nerve endings. This inhibition does not appear to be mediated by calmodulin or by dopamine receptors.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Benishin CG,Krueger BK,Blaustein MPsubject
Has Abstractpub_date
1988-02-01 00:00:00pages
195-201issue
2eissn
0026-895Xissn
1521-0111journal_volume
33pub_type
杂志文章abstract：:We determined the effect of flufenamic acid (FFA) and related derivatives on gap junction channel currents, applying the dual whole-cell patch-clamp technique to pairs of N2A neuroblastoma cells transfected with various connexins. FFA reduced gap junction channel currents in a reversible and concentration-dependent ma...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.6.1389
更新日期：2003-06-01 00:00:00
abstract：:Glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein is a costimulatory molecule that plays a role in inflammation so that GITR-Fc fusion protein can exert an anti-inflammatory effect. To investigate the mechanism by which GITR-Fc exerts its effects, we first used GITR knock-out (GITR(-/-)) mic...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.044354
更新日期：2008-06-01 00:00:00
abstract：:A fusion protein consisting of the endothelin B (ET(B)) receptor and the enhanced green fluorescent protein (EGFP) in conjunction with Cyanin3- or fluorescein-conjugated endothelin 1 (Cy3-ET1, Fluo-ET1) was used to investigate the ligand-mediated internalization of the ET(B) receptor. The ET(B) receptor and the ET(B)/...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:SC-54628 [1-(2-methylphenyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H- tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one] and its 1-(2,6-dimethylphenyl)-2H-imidazol-2-one derivative SC-54629 were potent inhibitors of 125I-angiotensin II (125I-AII) binding to rat adrenal cortex angiotensin type 1 (AT1) receptors. SC-...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:The immunosuppressive agent cyclosporine A has been shown to reverse multidrug resistance (MDR) in malignant cells. In the present study, a 3H-cyclosporine diazirine analogue was used to photolabel viable MDR Chinese hamster ovary cells. The 170-kDa membrane P-glycoprotein, which functions as a drug efflux pump, was s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-10-01 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：:The small GTPase Rac1 has been widely implicated in mammary tumorigenesis and metastasis. Previous studies established that stimulation of ErbB receptors in breast cancer cells activates Rac1 and enhances motility via the Rac-guanine nucleotide exchange factor P-Rex1. As the Janus tyrosine kinase 2 (Jak2)/signal trans...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.084293
更新日期：2013-05-01 00:00:00
abstract：:The aptamer mechanism of action involves the direct interaction of oligonucleotide with protein and is responsible for the biological effects of many pharmacologically active oligodeoxynucleotides. In the work reported here, we have determined the effects of aptamers on the secondary, tertiary, and quaternary structur...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:3H-Neurokinin A (3H-NKA) with high specific activity (75 Ci/mmol) was synthesized to study NKA (NK-2)-binding sites on membrane preparations of various tissues in the rat, including brain, spinal cord, duodenum, vas deferens, and ileum. The binding capacity of 3H-NKA (0.9 nM) was very low in membrane preparations of d...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:Phosphorylation of tau protein promotes stability of the axonal cytoskeleton; aberrant tau phosphorylation is implicated in the biogenesis of paired helical filaments (PHF) seen in Alzheimer's disease. Protein kinases and phosphatases that modulate tau phosphorylation have been identified using in vitro techniques; ho...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:The activities of phosphorylase kinase and myosin light-chain kinase are regulated by Ca2+ binding to calmodulin. However, differences in the activation properties of the purified enzymes are apparent, since calmodulin binds to phosphorylase kinase in the absence of Ca2+ whereas prior formation of a Ca2+ . calmodulin ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:The L-type amino acid transporter 1 (LAT1) is an Na(+)-independent neutral amino acid transporter subserving the amino acid transport system L. Because of its broad substrate selectivity, system L has been proposed to be responsible for the permeation of amino acid-related drugs through the plasma membrane. To underst...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.4.729
更新日期：2002-04-01 00:00:00
abstract：:We examined the role of putative trafficking sequences in two GABA(A) receptor subunits: α4 and δ. These subunits assemble with a β subunit to form a subtype of GABA(A) receptor involved in generating the "tonic" outward current. Both α4 and δ subunits contain dibasic retention motifs in homologous positions. When bas...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.092791
更新日期：2014-07-01 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 mammalian copper transporter 1 (CTR1) is responsible for the uptake of copper from the extracellular space. In this study, we used an isogenic pair of CTR1(+/+) and CTR1(-/-) mouse embryo fibroblasts to examine the contribution of CTR1 to the influx of cisplatin (DDP), carboplatin (CBDCA), oxaliplatin (L-OHP), and...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.052381
更新日期：2009-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.080689
更新日期：2013-01-01 00:00:00
abstract：:KARs, new semisynthetic antitumor bis-indole derivatives, were found to be inhibitors of tubulin polymerization with lower toxicity than vinblastine or vincristine, used in chemotherapy. Here, we compare the effect of KARs with those of vinblastine and vincristine on cell viability, cell proliferation, and cell cycle ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.60.6.1235
更新日期：2001-12-01 00:00:00
abstract：:All five (m1-m5) muscarinic receptors are sensitive to allosteric regulation, but gallamine is considerably more potent in slowing the dissociation of N-[3H]methylscopolamine (NMS) from the m2 subtype than from the m3 or m5 subtypes. To study the structural basis for the preference of gallamine for the m2 subtype, we ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:The nonselective cation channel TRPA1 (ANKTM1, p120) is a potential mediator of pain, and selective pharmacological modulation of this channel may be analgesic. Although several TRPA1 activators exist, these tend to be either reactive or of low potency and/or selectivity. The aim of the present study, therefore, was t...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.042663
更新日期：2008-04-01 00:00:00
abstract：:Olanzapine was shown to be oxidized to a reactive intermediate by HOCl, which is the major oxidant produced by activated neutrophils. A mass spectrum obtained using a flow system in which the reactants were fed into a mixing chamber and the products flowed directly into a mass spectrometer revealed a reactive intermed...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-06-01 00:00:00
abstract：:Norcocaine nitroxide and N-hydroxynorcocaine were found to stimulate hepatic microsomal lipid peroxidation in vitro, as measured by spin-trapping techniques using the spin trap alpha-[4-pyridyl-1-oxide]-N-tert-butylnitrone. It was determined that either norcocaine nitroxide or N-hydroxynorcocaine markedly enhanced the...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:We reported previously that protein associated with Myc (PAM) interacts with the C2 domain of type V adenylyl cyclase (ACV-C2) and that purified PAM is a potent inhibitor of Galphas-stimulated ACV activity (J Biol Chem 276:47583-47589, 2001). The present study was conducted to identify the region in PAM that inhibits ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.005355
更新日期：2005-01-01 00:00:00
abstract：:Signaling by G-protein-coupled receptors is often considered a uniform process, whereby a homogeneously activated proportion of randomly distributed receptors are activated under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, the...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.115.100248
更新日期：2015-09-01 00:00:00
abstract：:Capsaicin (vanilloid) sensitivity has long served as the functional signature of a subset of nociceptive sensory neurons. Mutagenesis studies have revealed seemingly distinct regions involved in mediating ligand binding and channel activation at the capsaicin binding site. Residue 547 (transmembrane region 4) mediates...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.023945
更新日期：2006-09-01 00:00:00
abstract：:Cytokines are thought to cause the depression of cytochrome P-450 (CYP)-associated drug metabolism in humans during inflammation and infection. We have examined the role of five cytokines, i.e., interleukin-1 beta, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma, on the expression of CY...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-10-01 00:00:00
abstract：:G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107854
更新日期：2017-09-01 00:00:00
abstract：:The response of myeloid leukemia cells to treatment with 1-beta-D-arabinofuranosylcytosine (ara-C) includes activation of the c-Abl protein tyrosine kinase and the stress-activated protein kinase (SAPK). The present studies demonstrate that treatment of human U-937 leukemia cells with ara-C is associated with transloc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.6.1489
更新日期：2002-06-01 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：:Activation of synthesis-modulating dopamine autoreceptors by dopamine or its agonists has been shown to inhibit dopamine synthesis in the rat striatum. However, systemic administration of the direct-acting dopamine agonist apomorphine failed to inhibit dopamine synthesis in striata from rats that had received local un...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:An opioid-like receptor has been cloned by several groups of researchers and recently shown to be activated by an endogenous heptadecapeptide termed orphanin FQ (or nociceptin). We isolated the corresponding mouse cDNA and coexpressed it in Xenopus laevis oocytes with the potassium channel subunits Kir3.1 (GIRK1) and ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
