Abstract：
:SR33557 belongs to a new class of molecules (indolizinsulfones) that act on the same receptor complex that has been characterized for other classical calcium channel effectors. The main binding properties of SR33557 to rabbit skeletal muscle are as follows. (i) Unlabeled SR33557 completely inhibits the specific binding of all classes of calcium channel antagonists such as dihydropyridines [(+)-[3H]PN200-110], phenylalkylamines ([3H] verapamil), benzothiazepines (d-(cis)-[3H]diltiazem), and diphenybutylpiperidines ([3H]fluspirilene). In all these cases inhibition of binding is of a noncompetitive nature. (ii) [3H]SR33557 binds with high affinity to T tubule membranes (KD = 0.08 nM) and the maximum binding capacity (Bmax = 78 pmol/mg of protein) is the same as that found for other classes of Ca2+ channel antagonists. Photoaffinity labeling confirms that [3H]SR33557 associates with the same protein of Mr 165,000 that binds the classical calcium channel inhibitors. 45Ca2+ uptake experiments performed with the rat aortic cell line A7r5, the insulin-secreting cell line RINm5F, and the pheochromocytoma cell line PC12 demonstrate that SR33557 fully inhibits the 1,4-dihydropyridine-sensitive 45Ca2+ uptake elicited by depolarization. A very good correlation was found between inhibition of 45Ca2+ uptake and of [3H]dopamine release in PC12 cells and between inhibition of 45Ca2+ uptake and of L-type Ca2+ current in A7r5 cells under whole-cell patch-clamp conditions.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Schmid A,Romey G,Barhanin J,Lazdunski Msubject
Has Abstractpub_date
1989-06-01 00:00:00pages
766-73issue
6eissn
0026-895Xissn
1521-0111journal_volume
35pub_type
杂志文章abstract：:We previously demonstrated that murine bone marrow stromal cells express high levels of cytochrome P4501B1 (CYP1B1) that metabolizes 7,12-dimethylbenza[a]anthracene (DMBA), and that DMBA activates the Ah receptor (AhR) in these cells in vitro. More recently, we reported that CYP1B1 is required for DMBA-induced lymphob...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.56.6.1317
更新日期：1999-12-01 00:00:00
abstract：:Neuroactive steroids bind to a unique site on the gamma-aminobutyric acidA (GABAA) receptor complex and allosterically modulate the binding of convulsant ([35S]t-butylbicyclophosphorothionate, [35S]TBPS), GABA ([3H]muscimol), and benzodiazepine ([3H]flunitrazepam) site ligands. In rat cortical membranes, 3 alpha-hydro...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine; (S)-HPMPC] is an antiviral drug that has been approved for the treatment of cytomegalovirus retinitis in patients with AIDS. Cidofovir also possesses potent activity against human papillomavirus-induced tumors in animal models and patients. We have recent...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.026559
更新日期：2007-03-01 00:00:00
abstract：:The levels of hepatic mRNAs for several enzymes involved in drug metabolism were measured following administration to rats of either phenobarbitone or 2-allyl-2-isopropylacetamide. There was a substantial elevation in the mRNA levels for cytochromes P450 IIB1, IIB2, and IIIA1, epoxide hydrolase, glutathione-S-transfer...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：:The aliphatic adenine analogues, D-eritadenine, L-eritadenine, L-threoeritadenine, and 9-(S)-(2,3-dihydroxypropyl)adenine [(S)DHPA] function as inhibitors/inactivators of purified S-adenosylhomocysteine (AdoHcy) hydrolase, but these compounds did not induce reduction of enzyme-bound NAD+. D-Eritadenine, L-eritadenine,...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:The toxicity of acetaminophen (4'-hydroxyacetanilide), 3,5-dimethylacetaminophen (3'-5'-dimethyl-4'-hydroxyacetanilide), and 2,6-dimethylacetaminophen (2',6'-dimethyl-4'-hydroxyacetanilide) was investigated in hepatocytes isolated from phenobarbital-pretreated rats. At a concentration of 5 mM, acetaminophen was found ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-06-01 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：:Magnesium modulates hormone-sensitive adenylate cyclase activation. In the present studies, we have examined the magnesium requirement of beta-adrenergic-stimulated adenylate cyclase activity in permeabilized human lymphocytes. Following isoproterenol pretreatment, under conditions that lead to homologous beta-adrener...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-03-01 00:00:00
abstract：:Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subt...
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
abstract：:[3H]Dihydroalprenolol ([3H]DHA) has been used extensively in receptor binding studies to measure beta-adrenergic receptors in the central nervous system. Usually, nonspecific binding has been defined by high concentrations of the beta-adrenergic receptor agonist isoproterenol or antagonists such as alprenolol or propr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:The P2Y(1) receptor is responsible for the initiation of platelet aggregation in response to ADP and plays a key role in thrombosis. Although this receptor is expressed early in the platelet lineage, the regulation of its expression during megakaryocyte differentiation is unknown. In the mouse megakaryocytic cell line...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.60.5.1112
更新日期：2001-11-01 00:00:00
abstract：:The present study investigates mRNA and protein levels of A3 adenosine receptors in resting (R) and activated (A) human lymphocytes. The receptors were evaluated by the antagonist radioligand [3H]5-N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2(2furyl)-pyrazolo-[4,3e]-1,2,4-triazolo-[1,5-c]-pyrimidine ([3H]MRE 3008F20)...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.3.711
更新日期：2004-03-01 00:00:00
abstract：:At central excitatory synapses, the transient elevation of intracellular calcium reduces N-methyl-D-aspartate (NMDA) receptor activity. Such 'calcium-dependent inactivation' is mediated by interactions of calcium/calmodulin and alpha-actinin with the C terminus of NMDA receptor 1 (NR1) subunit. However, inactivation i...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.3.595
更新日期：2002-03-01 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：:Intermediate-conductance (KCa3.1) and small-conductance (KCa2) calcium-activated K+ channels are gated by calcium binding to calmodulin (CaM) molecules associated with the calmodulin-binding domain (CaM-BD) of these channels. The existing KCa activators, such as naphtho[1,2-d]thiazol-2-ylamine (SKA-31), 6,7-dichloro-1...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.117.109421
更新日期：2017-10-01 00:00:00
abstract：:Guanine nucleotides have been examined as to their effects on subclass-specific excitatory amino acid receptor-ligand interactions. Guanine nucleotides selectively inhibit L-[3H]glutamate binding to the N-methyl-D-aspartate (NMDA) recognition site while showing a lesser effect on [3H]kainate, [3H]alpha-amino-3-hydroxy...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:Bovine pulmonary artery endothelial (CPAE) cells respond to bradykinin, and it has been suggested that the receptors on these cells do not fall into the normal B1/B2 classification of bradykinin receptors [J. Pharmacol. Exp. Ther. 244:646-649 (1988)]. The present study describes a detailed characterization of the subt...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Ca2-dependent protein phosphorylations activated by calmodulin or phospholipid were studied using selective inhibitors. Both protein phosphorylations were inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives. Kinetic analysis indicated that the primary effect of these agents was me...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
abstract：:Immune-mediated drug hypersensitivity reactions (IDHRs) represent a significant problem due to their unpredictable and severe nature, as well as the lack of understanding of the pathogenesis. Sulfamethoxazole (SMX), a widely used antibiotic, has been used as a model compound to investigate the underlying mechanism of ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.043273
更新日期：2008-06-01 00:00:00
abstract：:Rat and human lung microsomal cytochrome P-450 (P-450) enzymes have been characterized with regard to their catalytic activities towards several xenobiotic chemicals, including procarcinogens, in different microsomal preparations. Rat lung microsomal P-450s were more active than the human P-450s in catalyzing most of ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-05-01 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：:Diarylsulfonylurea (DSU) antitumor agents represent a new class of oncolytic compounds with an unknown, potentially novel, mechanism of action. At high concentrations of several of these agents, cytotoxicity appears to be a consequence of uncoupling of mitochondria. However, the mechanism of action at pharmacologicall...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:A nonnaturally occurring L-configuration nucleoside analog, L-beta-5-bromovinyl-(2-hydroxymethyl)-1,3-(dioxolanyl)uracil (L-BVOddU) selectively inhibited varicella-zoster virus growth in human embryonic lung (HEL) 299 cell culture with an EC(50) of 0.055 microM, whereas no inhibition of CEM and HEL 299 cell growth or ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.5.1109
更新日期：2000-11-01 00:00:00
abstract：:S-Adenosylmethionine (SAMe) and its metabolite 5'-methylthioadenosine (MTA) inhibit mitogen-induced proliferative response in liver and colon cancer cells. SAMe and MTA are also proapoptotic in liver cancer cells by selectively inducing Bcl-x(S) expression. The aims of this work were to assess whether these agents are...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.054411
更新日期：2009-07-01 00:00:00
abstract：:PC-12 cells, derived from a rat pheochromocytoma, were found to take up tritiated serotonin ([3H]5-HT) from the external medium by means of a saturable mechanism which follows Michaelis-Menten kinetics. The apparent Km of uptake was 0.39 microM and the Vmax was 0.40 pmole/min/10(6) cells. The uptake was temperature-de...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:Two human ovarian cancer cell lines were established from a patient before (PEO1) and after (PEO4) the onset of resistance to 5-fluorouracil (5-FU)/cisplatin-based chemotherapy. Using growth inhibition assays, we determined that the PEO4 line was almost 5-fold more resistant to 5-FU than the PEO1 line. The addition of...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-09-01 00:00:00
abstract：:A1 adenosine receptors in bovine cerebral cortex have been solubilized and subjected to sedimentation analysis using sucrose density gradient centrifugation. Because the receptors bound both agonists and antagonists with high affinity after solubilization, receptors labeled with an agonist or an antagonist radioligand...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:We demonstrate that gastrin-releasing peptide (GRP) can inhibit the proliferation of human immortal nontumorigenic (184-B5) mammary epithelial cells ectopically expressing the human GRP receptor. Growth of Balb 3T3 cells ectopically expressing relatively high levels of the GRP receptor was also inhibited by GRP; howev...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-03-01 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：:The biliary excretion of several organic anions is mediated by the canalicular multispecific organic anion transporter (cMOAT), which is hereditarily defective in mutant rats such as Eisai hyperbilirubinemic rats (EHBR). In addition, using a kinetic study with isolated canalicular membrane vesicles, we recently sugges...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-06-01 00:00:00
