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 sustained phase of [Ca2+]c was dependent on extracellular calcium. At lower concentrations, PDGF induced oscillatory changes in [Ca2+]c, and reduction of extracellular calcium attenuated the oscillation. An antiallergic compound, tranilast, abolished the sustained phase of [Ca2+]c induced by 1 nM PDGF. Tranilast also inhibited the oscillatory changes in [Ca2+]c induced by 200 pM PDGF. In addition, PDGF-induced calcium influx in the late G1 phase, as assessed by measuring the initial uptake of 45Ca, was inhibited by tranilast in a concentration-dependent manner. Tranilast also inhibited PDGF-augmented DNA synthesis; the ID50 for the inhibition of DNA synthesis was nearly identical to that for calcium influx. Although tranilast blocked PDGF-induced calcium entry, it did not affect PDGF-mediated autophosphorylation of the PDGF receptor, activation of phosphatidylinositol 3-kinase, activation of Ras or mitogen-activated protein kinase. Similarly, PDGF-induced elevation of diacylglycerol was not affected by tranilast. These results suggest that the antiallergic drug tranilast inhibits PDGF-induced DNA synthesis by blocking PDGF-mediated calcium entry. Tranilast may be of use in controlling PDGF-induced DNA synthesis in VSMC.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Nie L,Mogami H,Kanzaki M,Shibata H,Kojima Isubject
Has Abstractpub_date
1996-10-01 00:00:00pages
763-9issue
4eissn
0026-895Xissn
1521-0111journal_volume
50pub_type
杂志文章abstract：:Many Gi-coupled receptors are known to interact with the pertussis toxin (PTX)-insensitive Gz protein. Given that the alpha subunits of Gi and Gz share only 60% identity in their amino acid sequences, their receptor-interacting domains must be highly similar. By swapping the carboxyl termini of alpha i2 and alpha z wi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.1.38
更新日期：1997-07-01 00:00:00
abstract：:Binding of [3H](d)-N-allylnormetazocine ([3H](d)-NANM) to rat brain membranes is stereospecific, reversible, and saturable (Bmax = 260 fmol/mg of protein) and manifests moderately high affinity (Kd = 20 nM). The rank order of potency among opioidbenzomorphans and phencyclidine (PCP) analogs for competition for [3H](d)...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Two structural models have been developed to explain how agonist binding leads to ionotropic glutamate receptor (iGluR) activation. At alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) iGluRs, full and partial agonists close the agonist-binding domain (ABD) to different degrees whereas agonist-induced do...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.054254
更新日期：2009-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-02-01 00:00:00
abstract：:Opioid analgesics are used extensively in the management of pain. Although the clinically effective opioids bind with high affinity to the mu-opioid receptor, studies have suggested that the delta-opioid agonists might represent more ideal analgesic agents, with fewer side effects. A limitation to opiate effectiveness...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.2.272
更新日期：1997-08-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.62.1.15
更新日期：2002-07-01 00:00:00
abstract：:There is no approved means to prevent the toxic actions of cocaine. Cocaine esterase (CocE) is found in a rhodococcal strain of bacteria that grows in the rhizosphere soil around the coca plant and has been found to hydrolyze cocaine in vitro. The esteratic activity of CocE (0.1-1.0 mg, i.v.) was characterized and con...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.025999
更新日期：2006-12-01 00:00:00
abstract：:Both human ether-à-go-go-related gene (hERG1) and the closely related human ether-à-go-go (hEAG1) channel are aberrantly expressed in a large proportion of human cancers. In the present study, we demonstrate that transfection of hERG1 into mouse fibroblasts is sufficient to induce many features characteristic of malig...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.091439
更新日期：2014-08-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:Reconstitution experiments with purified components reproduce the basic characteristics of receptor/G protein coupling, i.e., GTP-sensitive high affinity agonist binding and receptor-promoted GTP binding. However, the interaction of agonists with the A1 adenosine receptor in rat and bovine but not human brain membrane...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:Most anticancer drugs have their origin in traditional medicinal plants. We describe here a flavone, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF), from the leaves of the Thai plant Gardenia obtusifolia, that has anti-inflammatory and anticancer potential. Because the nuclear factor-κB (NF-κB) pathway is linked ...
journal_title：Molecular pharmacology
pub_type： 杂志文章,收录出版
doi：10.1124/mol.110.067512
更新日期：2011-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：:Cytotoxic effects of quinones are thought to be mediated by redox cycles between quinones and quinols whereby reactive oxygen species are generated. The role of glucuronidation in preventing these toxic redox cycles was investigated by using benzo(a)pyrene-3,6-quinone and isolated rat hepatocytes or Reuber hepatoma ce...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-04-01 00:00:00
abstract：:The 5'-flanking region of the mouse mu opioid receptor (MOR) gene has two promoters, referred to as distal and proximal. MOR mRNA is predominantly initiated by the proximal promoter. Previously, several important cis-elements and trans-factors have been shown to play a functional role in the proximal promoter of the M...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.008284
更新日期：2005-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.003269
更新日期：2004-10-01 00:00:00
abstract：:We previously reported that angiotensin II (Ang II) increases cGMP content through a new Ang II receptor subtype that is distinct from both the AT1 and AT2 subtypes in differentiated Neuro-2A cells. In this study, the mechanism of the Ang II-stimulated cGMP increase was investigated in comparison with bradykinin- and ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:In saturation studies with [3H]dihydromorphine, unlabeled D-Ala2-D-Leu5-enkephalin (1 nM) inhibited the high-affinity binding component far more potently than the lower-affinity one. Similarly, morphine (1 nM) inhibited the higher-affinity binding of 3H-D-Ala2-D-Leu5-enkephalin to a greater extent than its lower-affin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:Very few antagonists have been identified for the human pregnane X receptor (PXR). These molecules may be of use for modulating the effects of therapeutic drugs, which are potent agonists for this receptor (e.g., some anticancer compounds and macrolide antibiotics), with subsequent effects on transcriptional regulatio...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.049437
更新日期：2008-09-01 00:00:00
abstract：:Human serum butyrylcholinesterase (Hu BChE) is a promising therapeutic against the toxicity of chemical warfare nerve agents. We have showed previously that recombinant (r) Hu BChE can be expressed at very high levels, 400 to 600 U/ml in mouse blood, by delivering the Hu BChE gene using adenovirus (Ad). Here, we repor...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.055665
更新日期：2009-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.5.1165
更新日期：2001-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.062018
更新日期：2010-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.054858
更新日期：2009-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-10-01 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：:Ribavirin used in therapies against hepatitis C virus (HCV) is potentially efficient against other viruses but presents a high cytotoxicity. Several ribavirin triphosphate analogs modified on the ribose moiety were synthesized and tested in vitro on the RNA polymerases of HCV, phage T7, and HIV-1 reverse transcriptase...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.63.3.538
更新日期：2003-03-01 00:00:00
abstract：:The precise mechanism by which the broad-spectrum anti-RNA virus agent ribavirin elicits its in vitro antiviral effect has remained a matter of debate. We have demonstrated that inhibition of cellular inosine monophosphate dehydrogenase (IMPDH) activity, and thus depletion of intracellular GTP pools, is the predominan...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.020057
更新日期：2006-04-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:We describe here an approach to characterize various lesions induced in DNA by drug treatments, using three parameters: (a) release of single-stranded DNA fragments by cell lysis in dilute alkali, which result from enzymatic strand scission during DNA repair or chemical alterations of DNA; (b) the presence of high mol...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-07-01 00:00:00
abstract：:It has been suggested that elevated cytosolic free calcium plays a key role in acetaminophen-induced cell death. The present study has examined the effect of a toxic concentration of acetaminophen on cytosolic free calcium in single mouse hepatocytes, using the dye fura-2 and video imaging fluorescence microscopy. Cyt...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
