Abstract：
:Chimeric receptors of the beta2-adrenergic receptor in which the extracellular loops were replaced with the corresponding amino acids of the alpha1a-adrenergic receptor were generated to measure changes in alpha1-antagonist affinity. Although no changes in alpha1-antagonist affinity were measured in the beta2/alpha1a chimeras, a decreased IC50 (10-fold) for agonists as compared with wild type beta2 control was found because of the replacement of the third extracellular loop (EX3). These agonist high affinity changes were because of a greater proportion of high affinity sites (2-fold) that were convertible to low affinity sites with guanosine 5'-3-O-(thio)triphosphate. Adenylate cyclase activity evoked by the EX3 chimera showed commensurate increases in the basal signal transduction as well as the isoproterenol-stimulated potency, suggesting constitutive activity. However, unlike other constitutively active adrenergic receptor mutants in which the mutation causes G protein-independent changes, the mechanism of the EX3 chimera seems to be attributable to a greater ease with which the active ternary complex is formed because of a higher affinity/coupling of the G protein. Although the changes because of EX3 are indirect and most likely affect helical packing, they support an emerging hypothesis that G protein-coupled receptors have evolved their structure-function relationships to constrain the receptor in an inactive state.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Zhao MM,Gaivin RJ,Perez DMdoi
10.1124/mol.53.3.524subject
Has Abstractpub_date
1998-03-01 00:00:00pages
524-9issue
3eissn
0026-895Xissn
1521-0111journal_volume
53pub_type
杂志文章abstract：:Functional coupling between muscarinic (m3) receptors and two voltage-gated K+ (Kv) channels (Kv1.2 and Kv1.5) cloned originally from canine colonic smooth muscle was studied using the Xenopus oocytes expression system and a mammalian cell line (COS cells). Oocytes were coinjected with cRNAs encoding the human m3 rece...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:Reversal of the multidrug-resistant (MDR) phenotype is very important for chemotherapy success. In fact, the expression of the MDR1 gene-encoded P-glycoprotein (P-gp) actively expels antitumor agents such as daunomycin (DNM) out of the cells, resulting in drug resistance. We show that upon conjugation to triplex-formi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.042010
更新日期：2008-05-01 00:00:00
abstract：:Bioassay-guided fractionation was used to isolate the lignan polygamain as the microtubule-active constituent in the crude extract of the Mountain torchwood, Amyris madrensis. Similar to the effects of the crude plant extract, polygamain caused dose-dependent loss of cellular microtubules and the formation of aberrant...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.075838
更新日期：2012-03-01 00:00:00
abstract：:The mouse 5-hydroxytryptamine4a (5-HT4a) receptor is an unusual member of the G protein-coupled receptor superfamily because it possesses two separate carboxyl-terminal palmitoylation sites, which may allow the receptor to adopt different conformations in an agonist-dependent manner (J Biol Chem 277:2534-2546, 2002). ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.008748
更新日期：2005-05-01 00:00:00
abstract：:Many human cancers show constitutive or amplified expression of the transcriptional regulator and oncoprotein Myc, making Myc a potential target for therapeutic intervention. Here we report the down-regulation of Myc activity by reducing the availability of Max, the essential dimerization partner of Myc. Max is expres...
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
abstract：:Regulator of G protein signaling (RGS) proteins accelerate the endogenous GTPase activity of Galpha(i/o) proteins to increase the rate of deactivation of active Galpha-GTP and Gbetagamma signaling molecules. Previous studies have suggested that RGS proteins are more effective on less efficiently coupled systems such a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.043547
更新日期：2008-05-01 00:00:00
abstract：:The gamma-aminobutyric acid-A (GABA(A)) receptor complex is allosterically modulated by a variety of substances, some of clinical importance. Barbiturates and neurosteroids augment GABA-currents and also directly gate the channel. A variety of gamma-butyrolactone analogues also modulate GABA-induced currents, with som...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.1.114
更新日期：1997-07-01 00:00:00
abstract：:The orphan nuclear receptor liver receptor homolog 1 (LRH-1; NR5A2) is a potent regulator of cholesterol metabolism and bile acid homeostasis. Recently, LRH-1 has been shown to play an important role in intestinal inflammation and in the progression of estrogen receptor positive and negative breast cancers and pancrea...
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
abstract：:n-Dodecylguanidine (C12-G) is an amphipathic compound with a guanidine moiety, which is positively charged at physiological pH, and a hydrophobic side chain. Its effects on an A-type K+ channel clone (rKv1.4) expressed in Xenopus oocytes were examined. C12-G caused a concentration-dependent (1-20 microM) positive shif...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-07-01 00:00:00
abstract：:Mitsuya and Broder [Proc. Natl. Acad. Sci. USA 83:1911-1915 (1986)] demonstrated that every purine (adenosine, guanosine, and inosine) and pyrimidine (cytidine and thymidine) nucleoside containing the 2',3'-dideoxyribose configuration, when evaluated against human immunodeficiency virus (HIV) in vitro, significantly s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:Expression vectors were designed and constructed to achieve optimum production of two different isozymes of rat glutathione S-transferase (GST) (EC 2.5.1.18) in COS cells, for studies of drug resistance. Promoter-enhancer elements from the simian virus 40 (SV40) early-region or the mouse alpha 2(I)-collagen gene, GST ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:Recombinant rat D3 dopamine receptors heterologously expressed in Chinese hamster ovary (CHO) cells are functionally coupled to endogenous G proteins. The affinity of the receptors for agonists is regulated by guanine nucleotides in the same manner as that of other G protein-linked receptors. The magnitude of the chan...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:The tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a vascular endothelial growth factor (VEGF) receptor-2 antagonist, has been used previously either alone or in combination with chemotherapeutic drugs for treating colorectal cancer in a mouse model. We analyzed the half-life of the peptide and found that because of degradation...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.119.117234
更新日期：2019-12-01 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：:The spatiotemporal dynamics of opioid signaling in the brain remain poorly defined. Photoactivatable opioid ligands provide a means to quantitatively measure these dynamics and their underlying mechanisms in brain tissue. Although activation kinetics can be assessed using caged agonists, deactivation kinetics are obsc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.088096
更新日期：2013-11-01 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：:Cytosolic liver acetyl-CoA:arylamine N-acetyltransferase (EC 2.3.1.5) from homozygous rapid acetylator rabbits (strain III/J) was purified to homogeneity as judged by gel filtration sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis and isoelectrofocusing. The isoelectric point was estimated to be 5.2. The...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-04-01 00:00:00
abstract：:Beta-adrenergic receptors were characterized in a particulate fraction of human auricles obtained from patients operated upon for coronary insufficiency or valvular disease. [125I] Hydroxybenzylpindolol binding was evaluated in terms of kinetics; KD and Bmax values; and inhibition of binding in the presence of 10 micr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:Because cytotoxicity by an alkylating agent such as N-methyl-N'-nitrosoguanidine is markedly increased in adenine methylase-deficient dam-3 Escherichia coli, it was of interest to assess whether mismatch repair was similarly important in the repair of DNA damage induced by cis-diamminedichloroplatinum(II) (CDDP). The ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. In this study, we report the ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107623
更新日期：2017-04-01 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
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：:Retroviral integrases are essential for viral replication and represent an attractive chemotherapeutic target. In the current study, we demonstrated the activity of micromolar concentrations of dinucleotides against human immunodeficiency virus type 1 (HIV-1), HIV type 2 (HIV-2), simian immunodeficiency virus, and fel...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.4.567
更新日期：1997-04-01 00:00:00
abstract：:Neuroactive steroids are efficacious potentiators of GABA-A receptors. Recent work has identified a site in the alpha1 subunit of the GABA-A receptor, that is essential for potentiation by steroids. However, each receptor contains two copies of the alpha1 subunit. We generated concatemers of subunits so that the alpha...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.053629
更新日期：2009-04-01 00:00:00
abstract：:The purpose of these studies was to support the hypothesis that an undiscovered cannabinoid receptor exists in brain. [(35)S]GTP gamma S binding was stimulated by anandamide and WIN55212-2 in brain membranes from both CB(1)(+/+) and CB(1)(-/-) mice. In contrast, a wide variety of other compounds that are known to acti...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-07-01 00:00:00
abstract：:The GABA type A receptor (GABA(A)R) is the major inhibitory receptor in the mammalian central nervous system and the target of numerous pharmaceuticals. The alpha-subunit of these pentameric Cys-loop neurotransmitter-gated ion channels contributes to the binding of both GABA and allosteric modulators such as the benzo...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.059832
更新日期：2010-07-01 00:00:00
abstract：:TWIK-related K(+) 1 (TREK1) potassium channels are members of the two-pore domain potassium channel family and contribute to background potassium conductances in many cell types, where their activity can be regulated by a variety of physiologic and pharmacologic mediators. Fenamates such as FFA (flufenamic acid; 2-{[3...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.091199
更新日期：2014-05-01 00:00:00
abstract：:The 5-hydroxytryptamine3 receptor 5-HT3R has been implicated in gut and cardiac motility and in behavioral disorders. Characteristics of 5-HT3Rs appear to be heterogeneous among species, but human 5-HT3R cDNA has not been identified. We isolated a cDNA encoding 5-HT3R from human hippocampus. The mouse 5-HT3R gene has ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:5-Hydroxytryptamine3 (5-HT3) receptors are ligand-gated ion channels that mediate neurotransmission by serotonin in the central nervous system. Pharmacological inhibition of 5-HT3 receptor activity has therapeutic potential in several psychiatric diseases, including depression and anxiety. The recently approved multim...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.118.113530
更新日期：2018-12-01 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
