Abstract:
:Catecholamine transporters constitute the biological targets for several important drugs, including antidepressants, cocaine, and related compounds. Some information exists about discrete domains of these transporters that are involved in substrate translocation and uptake blockade, but delineation of domains mediating the ionic dependence of the transport remains to be defined. In the present study, human neuronal transporters for dopamine and noradrenaline (hDAT and hNET) and a series of six functional chimeras were transiently expressed in LLC-PK1 cells. Substitution of Cl(-) by isethionate reveals that cassette IV (i.e., the region of the transporter encompassing transmembrane domain 9 through the COOH terminal) plays an important role in the Cl(-)- dependence of the uptake. Substitutions of Na(+) and NaCl by Tris(+) and sucrose, respectively, demonstrate that three different segments scattered across the transporter are involved in the Na(+)- dependence of the transport activity: cassette I (i.e., the region from the amino terminus through the first two transmembrane domains), cassette IV, and junction between transmembrane domains 3 to 5 and 6 to 8. Results of the present work also suggest that the use of Tris(+) as a substitute for Na(+) results in a biased estimate of the Hill number value for hDAT. This study provides useful clues for identifying specific residues involved in the uptake function of the catecholamine transporters.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Syringas M,Janin F,Mezghanni S,Giros B,Costentin J,Bonnet JJdoi
10.1124/mol.58.6.1404keywords:
subject
Has Abstractpub_date
2000-12-01 00:00:00pages
1404-11issue
6eissn
0026-895Xissn
1521-0111journal_volume
58pub_type
杂志文章abstract::Excitotoxin-induced destruction of striatal neurons, proposed as a model of Huntington's disease, involves a process having the biochemical stigmata of apoptosis. Recent studies suggested that transcription factor nuclear factor (NF)-kappa B may be involved in excitotoxicity. To further analyze the contribution of NF ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.53.1.33
更新日期:1998-01-01 00:00:00
abstract::The effects of tournefolic acid B (TAB) and two ester derivatives, TAB methyl ester (TABM) and TAB ethyl ester (TABE), on N-methyl-D-aspartate (NMDA)-mediated excitotoxicity and the underlying mechanisms were investigated. Treatment with 50 microM NMDA elicited neuronal death by 48.7 +/- 5.1%, coinciding with the appe...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.018770
更新日期:2006-03-01 00:00:00
abstract::The Notch family consists of four highly conserved transmembrane receptors. The release of the active intracellular domain requires the enzymatic activity of γ-secretase. Notch is involved in embryonic development and in many physiologic processes of normal cells, in which it regulates growth, apoptosis, and different...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/molpharm.120.000006
更新日期:2020-11-01 00:00:00
abstract::A substantial body of research implicates L-cysteine sulfinic acid (L-CSA) as a neurotransmitter. However, all physiological actions of L-CSA that have been pharmacologically characterized are mediated by cross-activation of glutamate receptors, and no receptor has been identified that is primarily activated by L-CSA....
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-06-01 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
abstract::Electrical recordings were made in Xenopus oocytes to study the modulatory effects of steroids on gamma-aminobutyric acid (GABA) receptors expressed by RNA from mammalian brain and retina. GABA responses expressed by rat cerebral cortex poly(A)+ RNA were bicuculline-sensitive Cl- currents mediated by GABAA receptors. ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::The structure-activity relationships for vasoactive intestinal peptide (VIP) receptor binding were studied using N-terminally modified VIP analogs. VIP fragments, and VIP receptor antagonists. Tissue sources included bovine coronary artery, rat mesenteric artery, rat pituitary, rat brain synaptosomes, and rat liver. E...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-06-01 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::Metyrapone administration to 21- and 90-day-old male rats causes a transcriptional induction of the hepatic glucocorticoid-inducible CYP3A1 gene within an hour as determined by nuclear run-on experiments. Analyses performed 24 hr after metyrapone administration in both ages of rat demonstrate that the transcriptional ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Antibodies against synthetic peptides of the D2 dopamine receptor were used, in combination with photoaffinity labeling, to localize the region of ligand binding in the receptor. Specific antibodies to peptide sequences 221-234 and 259-272 and to the carboxyl-terminal peptide 402-415, all corresponding to cytoplasmic ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
abstract::Ceramides are naturally occurring compounds recognized to mediate apoptosis. N-acylsphingosines, containing a double bond at carbons 4 and 5 of their sphingoid backbone, are thought to be the active form, because N-acylsphinganines with completely saturated sphingoid are inactive. In the present study, we synthesized ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.5.1249
更新日期:2001-05-01 00:00:00
abstract::The fluorogenic sulfhydryl probe 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) (1-50 nM) is used to characterize the functional role and location of highly reactive thiol groups on the ryanodine-sensitive Ca2+ release channel complex [i.e., ryanodine receptors (RyRs)] of skeletal and cardiac junctional...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::A polyamine component of Agelenopsis aperta spider venom designated FTX is reported to be a selective antagonist of P-type calcium channels in the mammalian brain. Consequently, this component has frequently been used as a pharmacological tool to determine the presence, distribution, and function of P-type channels in...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Several lines of evidence suggest that G-protein-coupled receptors can adopt different active conformations, but their direct demonstration in intact cells is still missing. Using a fluorescence resonance energy transfer (FRET)-based approach we studied conformational changes in alpha(2A)-adrenergic receptors in intac...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.052399
更新日期:2009-03-01 00:00:00
abstract::A conjugate molecule was synthesized by linking the DNA-intercalative antitumor drug 4'-(9-acridinylamino)methanesulfon-manisidide (mAMSA) via a 4-carboxamide side chain to a dipyrrolecarboxamide moiety structurally related to the minor groove-binding antibiotic netropsin. The molecule (netropsin/ mAMSA) behaves as a ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Gemcitabine and pemetrexed are effective agents in the treatment of non-small-cell lung cancer (NSCLC), and the present study investigates cellular and genetic aspects of their interaction against A549, Calu-1, and Calu-6 cells. Cells were treated with pemetrexed and gemcitabine, and their interaction was assessed usi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.009373
更新日期:2005-07-01 00:00:00
abstract::The NO/cGMP signaling pathway plays a major role in the cardiovascular system, in which it is involved in the regulation of smooth muscle tone and inhibition of platelet aggregation. Under pathophysiological conditions such as endothelial dysfunction, coronary artery disease, and airway hyperreactivity, smooth muscle ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.020909
更新日期:2006-06-01 00:00:00
abstract::The mitogen-activated protein kinase (MAPK) pathway plays a pivotal role in intracellular signaling, and this cascade may impinge on cAMP response elements (CREs) of target genes. Both the MAPK pathway and chromogranin A expression may be activated by cytosolic calcium influx, and calcium-dependent signals map onto th...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.54.1.59
更新日期:1998-07-01 00:00:00
abstract::The bile salt export pump (BSEP/ABCB11) transports bile salts from hepatocytes into bile canaliculi. Its malfunction is associated with severe liver disease. One reason for functional impairment of BSEP is systemic administration of drugs, which as a side effect inhibit the transporter. Therefore, drug candidates are ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.108688
更新日期:2017-10-01 00:00:00
abstract::Purified assembly-competent vimentin, an intermediate filament protein, was obtained from bovine lens in this study. The effects of withangulatin A on vimentin assembly with or without phosphorylation were examined by negative-stain electron microscopy. Soluble tetrameric vimentin was assembled into irregular fibrils ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::The binding affinities of 16 7-substituted 2,3-dichlorodibenzo-p-dioxins for the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cytosolic receptor protein from male Wistar rats have been determined. The EC50 value for each compound was estimated by competitive displacement of [3H]TCDD and the data illustrated that the dif...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-06-01 00:00:00
abstract::The effect of breast cancer resistance protein (Bcrp/Abcg2) on the disposition of the phytoestrogens daidzein, genistein, and coumestrol was investigated using Bcrp(-/-) mice. Expression of the genes for either mouse Bcrp or human BCRP in MDCK II cells induced apically directed transport of the three phytoestrogens, w...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.034751
更新日期:2007-10-01 00:00:00
abstract::Previous studies have shown that exposure of phenobarbital-pretreated rats to halothane in 10% O2 causes centrilobular necrosis, induces expression of the 72-kDa heat shock protein (HSP72), and produces several trifluoroacetylated adducts. In the present study the time course of development of the centrilobular lesion...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::An 'epoxygenase' eicosanoid analog, 14, 15-cis-episulfide-eicosatrienoic acid, has several unique pharmacological effects on platelets. These include (i) inhibition of ionophore A23187- but not thrombin-induced activation, (ii) inhibition of thromboxane B2 biosynthesis derived from endogenous but not exogenous arachid...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 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::UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1) catalyzes the glucuronidation of bilirubin in liver. Among all UGT isoforms identified to date, it is the only relevant bilirubin-glucuronidating enzyme in human. Because glucuronoconjugation is the major route of bilirubin elimination, any genetic alteration that affects...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.56.3.526
更新日期:1999-09-01 00:00:00
abstract::High expression of the aflatoxin B1 (AFB1)-8,9-epoxide-conjugating glutathione S-transferase A3 (mGSTA3) subunit in mouse liver confers intrinsic resistance to AFB1 hepatocarcinogenesis. It is not known how the gene encoding this protein is regulated. The murine mGSTA3 gene has been identified using bioinformatics. It...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.64.5.1018
更新日期:2003-11-01 00:00:00
abstract::Aldose reductase (AKR1B1) is a critical drug target because of its involvement in diabetic complications, inflammation, and tumorigenesis. However, to date, development of clinically useful inhibitors has been largely unsuccessful. Cyclopentenone prostaglandins (cyPGs) are reactive lipid mediators that bind covalently...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.100693
更新日期:2016-01-01 00:00:00
abstract::Effects of pimaric acid (PiMA) and eight closely related compounds on large-conductance K(+) (BK) channels were examined using human embryonic kidney (HEK) 293 cells, in which either the alpha subunit of BK channel (HEKBKalpha) or both alpha and beta1 (HEKBKalphabeta1) subunits were heterologously expressed. Effects o...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.62.4.836
更新日期:2002-10-01 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