Abstract：
:The dopamine D3 receptor, although structurally similar to the dopamine D2 receptor, has 100-fold higher affinity for agonists such as dopamine and quinpirole, when these receptors are expressed in 293 cells. Additionally, the D3 receptor has generally lower affinity for several antagonists than does the D2 receptor. To determine which regions of the receptor account for these differences, chimeras between D2 and D3 receptors were constructed in which intracellular loops were exchanged between the two receptors. A D2 receptor containing the third intracellular loop (IL3) from the D3 receptor had 10-20-fold higher affinity for dopamine and quinpirole than did the wild-type D2 receptor. Conversely, the D3 receptor containing the IL3 of the D2 receptor had 15-30-fold lower affinity for agonists than did the wild-type D3 receptor. That is, in these chimeras the IL3 shifted agonist affinity in a direction consistent with the agonist affinity of the receptor from which the IL3 was derived. In contrast, antagonist binding was not significantly altered. Chimeras in which the second intracellular loop was switched between the D2 and D3 receptors had essentially unchanged affinity for both agonists and antagonists. The data presented here suggest that structural differences in the IL3 of the D2 and D3 receptors partially account for observed differences in agonist binding to these receptors.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Robinson SW,Jarvie KR,Caron MGsubject
Has Abstractpub_date
1994-08-01 00:00:00pages
352-6issue
2eissn
0026-895Xissn
1521-0111journal_volume
46pub_type
杂志文章abstract：:Resveratrol (RES), a natural plant polyphenol, has gained interest as a nontoxic chemopreventive agent capable of inducing tumor cell death in a variety of cancer types. However, the early molecular mechanisms of RES-induced apoptosis are not well defined. Using the human breast cancer cell lines MDA-MB-231 and MCF-7,...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.039040
更新日期：2007-12-01 00:00:00
abstract：:We have identified alpha 2-adrenergic receptors on human erythroleukemia (HEL) cells, a suspension-grown cell line related to human platelets. properties of receptors were assessed in intact cells by binding of the antagonist [3H]yohimbine and by inhibition of cAMP accumulation. [3H]Yohimbine labeled 5900 +/- 2100 rec...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
abstract：:[3H]-d-cis-Diltiazem binds to canine cardiac sarcolemma in a specific, saturable, and reversible manner with a KD = 58.0 +/- 9.5 nM and a receptor site density (maximum binding) of 2.19 +/- 0.24 pmol/mg of protein. Bepridil and verapamil, Ca2+ channel inhibitors, can completely inhibit this binding at nM concentration...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
abstract：:Consequent to agonist exposure, many G protein-coupled receptors undergo sequestration or internalization. Results with receptors linked to adenylate cyclase, such as the beta 2-adrenergic receptor, or receptors linked to phospholipase C (PLC) have provided conflicting results regarding the role of second messenger-de...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 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
abstract：:Three different cDNA clones, namely DM1-1, Dah1, and Dah2, encoding hepatic cytochrome P-450, were isolated from a cDNA library in lambda gt11 constructed from liver RNA of polychlorinated biphenyl-treated beagle dogs. DM1-1 was 1857 base pairs (bp) long and encoded a polypeptide of 457 residues. Dah1 was 2394 bp long...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:In Rat-1 fibroblasts, endothelin-1 and a protein kinase C-stimulating phorbol ester stimulated extracellular signal-regulated kinase (ERK), whereas phenylephrine, acting at stably transfected human alpha1A-adrenoceptors, inhibited basal and endothelin-1- and phorbol ester-stimulated ERK. On the other hand, phenylephri...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.54.5.755
更新日期：1998-11-01 00:00:00
abstract：:In cells expressing both the insulin receptor isoform A (IRA) and the insulin-like growth factor-1 receptor (IGF1R), the presence of hybrid receptors, made up of an alphabeta-IRA chain associated with an alphabeta-IGF1R chain, has been demonstrated. These heterodimers are found in normal cells, and they also seem to p...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.026989
更新日期：2006-11-01 00:00:00
abstract：:In the human lymphocyte, desensitization of the beta-adrenergic receptor-adenylate cyclase complex is associated with sequestration of the receptor as well as a change in photolabeling of beta-receptor proteins. Thus, desensitization of the lymphocyte beta-adrenergic receptor-adenylate cyclase system is associated wit...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-11-01 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 role of mitogen-activated protein kinase signaling and the transcription factor c-Jun in epidermal growth factor (EGF)-induced expression of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. EGF increased the activation of extracellular signal-regulated kinase (ERK) and c-Jun amino terminal kin...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-01-01 00:00:00
abstract：:The aim of this study was to clarify the mechanism by which cytochrome P450 (P450)-mediated catalytic activity is decreased following interferon (IFN) administration. Microsomal steroid hydroxylation was assessed to test the hypothesis that IFN selectively decreases the activities of individual P450 isozymes in male r...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-09-01 00:00:00
abstract：:GABAA receptors are modulated by a variety of compounds, including the neurosteroids and barbiturates. Although the effects of barbiturates on alphabetagamma isoforms, thought to dominate phasic (synaptic) GABAergic inhibition, have been extensively studied, the effects of pentobarbital on kinetic properties of alphab...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.002543
更新日期：2004-10-01 00:00:00
abstract：:To study the molecular pharmacology of low-voltage-activated calcium channels in biophysical detail, human medullary thyroid carcinoma (hMTC) cells were investigated using the single-channel technique. These cells had been reported to express T-type whole-cell currents and a Ca(v)3.2 (or alpha 1H) channel subunit. We ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.3.682
更新日期：2002-03-01 00:00:00
abstract：:Dietary lipids and fat-soluble micronutrients are solubilized in mixed micelles and absorbed in the small intestine. Based on an assumption that cholesterol and other fat-soluble molecules share a number of transport mechanisms and the fact that Niemann-Pick C1-like 1 (NPC1L1) is critical for intestinal cholesterol ab...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.043034
更新日期：2008-07-01 00:00:00
abstract：:Using [3H]leukotriene C4 (LTC4) and radioligand-binding techniques, specific leukotriene C4 binding sites have been identified in membranes derived from guinea pig ventricular myocardium. High performance liquid chromatography analyses indicated that, in the presence of the gamma-glutamyl transpeptidase inhibitor L-se...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-02-01 00:00:00
abstract：:The nuclear receptor peroxisome proliferator-activated receptor (PPAR) is activated by a diverse group of acidic ligands, including many peroxisome proliferator chemicals present in the environment. Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling is activated by multiple cyt...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.2.355
更新日期：2003-08-01 00:00:00
abstract：:We have reported previously that the transmembrane domains of the cholecystokinin-B/gastrin receptor (CCK-BR) comprise a putative ligand binding pocket. In the present study, we examined whether amino acid substitutions within the CCK-BR pocket altered the affinities and/or functional activities of L-365,260 (the prot...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.54.5.857
更新日期：1998-11-01 00:00:00
abstract：:In previous studies, it was shown that the overexpression of beta2-adrenoceptor (beta2AR) in the hearts of transgenic mice (Tg) leads to agonist-independent activation of adenylate cyclase and enhanced myocardial function. Here, we measured the physical coupling of beta2AR and Gs by evaluating the coimmunoprecipitatio...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.2.187
更新日期：1997-08-01 00:00:00
abstract：:15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a cyclopentenonic prostaglandin endowed with powerful anti-inflammatory activities, as shown in animal models of inflammatory/autoimmune diseases, where pharmacological administration of this prostanoid can ameliorate inflammation and local tissue damage via act...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.038042
更新日期：2007-11-01 00:00:00
abstract：:Stimulation of alpha1-adrenoreceptors (alpha1-AR) acutely alters ion channel behavior via several signaling pathways [calcium and protein kinase C (PKC)]. Little is known about sustained alpha1-adrenergic/PKC signaling and channel regulation as may occur during cardiovascular disease states. Here we describe the effec...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.109.062216
更新日期：2010-08-01 00:00:00
abstract：:The human dopamine and norepinephrine transporters (hDAT and hNET, respectively) control neurotransmitter levels within the synaptic cleft and are the site of action for amphetamine (AMPH) and cocaine. We investigated the role of a threonine residue within the highly conserved and putative phosphorylation sequence RET...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.069039
更新日期：2011-03-01 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：: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：:Beta-L-dioxolane-cytidine (L-OddC, BCH-4556, Troxacitabine), a novel L-configuration deoxycytidine analog, is under phase III clinical trial for cancer treatment. We showed that human apurinic/apyrimidinic endonuclease (APE-1) has exonuclease activity for preferentially removing L-OddC and other L-configuration nucleo...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.021527
更新日期：2006-05-01 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：:Membrane trafficking of the δ-opioid receptor (DOR) from intracellular compartments to plasma membrane in central neurons, induced by various pathological conditions such as long-term opioid exposure, represents unique receptor plasticity involved in the mechanisms of long-term opioid effects in opioid addiction and o...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.076307
更新日期：2012-03-01 00:00:00
abstract：:beta-arrestins have been shown to play important roles in regulation of signaling and desensitization of opioid receptors in many in vivo studies. The current study was carried out to measure the direct interaction of beta-arrestins with two functional intracellular domains, the third intracellular loop (I3L) and the ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.4.758
更新日期：2001-04-01 00:00:00
abstract：:Several structurally related series of folate analogs were studied as substrates for mouse liver folylpolyglutamate synthetase (FPGS). A comparison of the kinetics of the interaction of this enzyme with folate analogs that contained the quinazoline ring in place of the pteridine ring with those of the analogous pterid...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:Many progestins have been developed for use in contraception, menopausal hormone therapy, and treatment of gynecological diseases. They are derived from either progesterone or testosterone, and they act by binding to the progesterone receptor (PR), a hormone-inducible transcription factor belonging to the nuclear rece...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.054312
更新日期：2009-06-01 00:00:00
