Abstract:
:Previous studies have established that two Xbal polymorphic restriction fragments [11.5 and 44 kilobases (kb)] hydridizing to a full length debrisoquin hydroxylase cDNA are associated with two different mutant alleles for the debrisoquin hydroxylase gene (IID6). An independent allele, defined by Xbal 16- and 9-kb fragments, has previously been identified only in extensive metabolizers, precluding determination of whether this restriction fragment length polymorphism (RFLP) pattern identifies a functional or nonfunctional mutant allele of IID6. We phenotyped and performed RFLP studies in the family of a poor metabolizer (PM) propositus with the Xbal 16 + 9 allele. Three family members were of the PM phenotype, two of whom had the 16 + 9 allele, indicating that this RFLP pattern identified a nonfunctional IID6 allele in this family. Moreover, additional RFLP analyses indicated that the PM mother had two different IID6 mutant alleles that produce the Xbal 29-kb fragment, indistinguishable from the RFLP pattern produced by a functional IID6 allele. These data indicate that the Xbal 16 + 9 RFLP pattern can identify a mutant IID6 allele and that at least two different nonfunctional mutant alleles can produce the Xbal 29-kb fragment found in all extensive metabolizers.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Evans WE,Relling MVsubject
Has Abstractpub_date
1990-05-01 00:00:00pages
639-42issue
5eissn
0026-895Xissn
1521-0111journal_volume
37pub_type
杂志文章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::Cardiac function is regulated by many hormones and neurotransmitters that exert their physiological effects through the activation of G protein-coupled receptors (GPCRs). Identification of new GPCRs that might display a specific pattern of expression within the heart and differentially regulate specific cardiac functi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.054155
更新日期:2009-05-01 00:00:00
abstract::delta-Opioid receptor (DOR) promoter exhibited a cell-type-specific expression pattern. Protein-DNA interactions in this promoter were identified by dimethyl sulfate in vivo footprinting analysis of NG108-15 cells, expressing endogenous DOR. Complete protection of the putative Sp1 cis-element and partial protection of...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.60.2.331
更新日期:2001-08-01 00:00:00
abstract::The effect of relatively nontoxic levels of HgCl2 on semiconservative DNA synthesis and on DNA repair induced following treatment of intact cells with X-ray or ultraviolet (UV) light has been studied in cultured Chinese hamster ovary cells. In the presence of 1 microM HgCl2 the repair of DNA strand breaks induced by 4...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-02-01 00:00:00
abstract::The nucleoside analog 5-azacytidine is an archetypical drug for epigenetic cancer therapy, and its clinical effectiveness has been demonstrated in the treatment of myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). However, therapy resistance in patients with MDS/AML remains a challenging issue. Mem...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.086801
更新日期:2013-09-01 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::We have investigated various nitric oxide (NO) synthase inhibitors for their affinity and selectivity toward the three human isoenzymes in radioligand binding experiments. Therefore, we developed the new radioligand [(3)H]2-amino-4-picoline to measure binding of these compounds to the three human NO synthase (NOS) iso...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::The epithelial sodium channel (ENaC) is believed to represent the rate-limiting step for sodium absorption in the renal collecting duct. Consequently, ENaC is a central effector affecting systemic blood volume and pressure. Sodium and water transport are dysregulated in diabetes mellitus. Peroxisome proliferator-activ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.056911
更新日期:2009-12-01 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::The deletion of Phe-508 (DeltaPhe508) constitutes the most prevalent of a number of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that cause cystic fibrosis (CF). This mutation leads to CFTR misfolding and retention in the endoplasmic reticulum, as well as impaired channel activity. The b...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.055608
更新日期:2009-06-01 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::Previous studies have shown that neural stimulation of brown adipose tissue (BAT) reorganizes the expression and activity of signaling proteins in the beta-adrenergic adenylyl cyclase pathway. Cold stress increases neural stimulation of BAT and increases alpha1-adrenergic receptor number; however, the alpha1 receptor ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.51.4.644
更新日期:1997-04-01 00:00:00
abstract::Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that are involved in lipid metabolism, differentiation, proliferation, cell death, and inflammation. Three subtypes have been identified: PPAR-alpha, -delta, and -gamma. We have previously shown presence of PPAR-gamma mRNA in the amn...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.64.6.1586
更新日期:2003-12-01 00:00:00
abstract::Effects of ethanol on the function of Ca(2+)-activated Cl- channels activated by G protein-coupled serotonin (5-hydroxytryptamine, (5-HT)1c) and muscarinic M1 cholinergic receptors were studied in Xenopus oocytes expressing mouse whole-brain mRNA. Ethanol (25-200 mM) inhibited currents evoked by both 5-HT and acetylch...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::Ro 11-2465 is a cyanide derivative of imipramine. In cerebral cortex homogenates, [3H] Ro 11-2465 displays a binding profile similar to that of [3H]imipramine. Agents compete with binding of [3H]Ro 11-2465 in an order of potency similar to their ability to block serotonin uptake, and raphe lesions greatly decrease the...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-05-01 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::We have observed that rodent cell lines (mouse, hamster) contain approximately 10 times the levels of dihydrofolate reductase as human cell lines, yet the sensitivity to methotrexate (ED(50)), the folate antagonist that targets this enzyme, is similar. Our previous studies showed that dihydrofolate reductase protein l...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.055772
更新日期:2009-10-01 00:00:00
abstract::At sites of inflammation, endothelial cells play a major role in defining the types of leukocytes that are recruited to a specific area. This is accomplished, at least in part, through the cytokine induction of cell surface adhesion molecules, including vascular cell adhesion molecule 1 (VCAM-1). We investigated the r...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::It has long been believed that the cortical actin cytoskeleton plays an important role in regulating the secretion of hormones and neurotransmitters. In this study, we investigated the control of actin dynamics in primary neuroendocrine cells and determined the relationship of actin dynamics to various components of t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.008474
更新日期:2005-04-01 00:00:00
abstract::Neuronal cell lines provide a source of pure populations of neurons and allow the properties of many neurotransmitter receptors to be studied. However, none of these cells have been reported to express functional gamma-aminobutyric acid (GABA)A receptors. Indeed, there have been no reports of cell lines expressing fun...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::In rat pancreatic zymogen granules (ZG), an ATP-sensitive K(+) conductance and a Cl(-) conductance have been characterized that are inversely regulated by an approximately 65-kDa multidrug resistance P-glycoprotein (mdr1) gene product. In search of a label for purification of this protein, we found that the dihydropyr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::The precise mechanism by which the cellular uptake of the endocannabinoid anandamide (AEA) occurs has been the source of much debate. In the current study, we show that neuronal differentiated CAD (dCAD) cells accumulate anandamide by a process that is inhibited in a dose-dependent manner by N-(4-hydroxyphenyl)arachid...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.044834
更新日期:2008-07-01 00:00:00
abstract::The renal outer medullary potassium channel (ROMK) is expressed in the kidney tubule and critically regulates sodium and potassium balance. The physiological functions of other inward rectifying K(+) (Kir) channels expressed in the nephron, such as Kir7.1, are less well understood in part due to the lack of selective ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.059840
更新日期:2009-11-01 00:00:00
abstract::Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN) to yield nitric oxide (NO) or a related species that activates soluble guanylate cyclase (sGC), resulting in cGMP-mediated vasodilation. Accordingly, established ALDH2 inhibitors attenuate GTN-induced vasorela...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.113.086835
更新日期:2013-09-01 00:00:00
abstract::The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectabl...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.040105
更新日期:2008-09-01 00:00:00
abstract::Cadmium is a dangerous metal distributed widely in the environment. Members of our laboratory recently identified the ZIP8 transporter protein, encoded by the mouse Slc39a8 gene, to be responsible for genetic differences in response to cadmium damage of the testis. Stable retroviral infection of the ZIP8 cDNA in mouse...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.024521
更新日期:2006-07-01 00:00:00
abstract::The cytotoxic efficacy of antitumor drugs targeted at DNA topoisomerase II (topo II) in many cases varies in direct proportion to cellular topo II content. To investigate the transcriptional control of the predominant alpha form of topo II, the 5' flanking region of the human topo II alpha gene (positions -562 to +90)...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::This study assessed how conformational information encoded by ligand binding to δ-opioid receptors (DORs) is transmitted to Kir3.1/Kir3.2 channels. Human embryonic kidney 293 cells were transfected with bioluminescence resonance energy transfer (BRET) donor/acceptor pairs that allowed us to evaluate independently reci...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.081950
更新日期:2013-02-01 00:00:00
abstract::The aryl hydrocarbon receptor (AhR) is a transcriptional enhancer that is activated by the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related toxic xenobiotics, as well as some naturally occurring compounds. Ligand binding initiates 1) dissociation of the ligand-bound monomeric AhR from the ligand-unocc...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Recently, several classes of compounds have been shown to be potent, selective, and specific inhibitors of human immunodeficiency virus type 1 replication in vitro. These include the tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione (TIBO) and the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (H...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00