Abstract：
:We have recently demonstrated that the alpha 2-adrenergic radioligand [3H]idazoxan also labels additional sites that do not recognize catecholamines but bind with high affinity several chemically distinct drugs previously assumed to be highly selective for alpha 2-adrenergic receptors [Mol. Pharmacol. 35:324-330 (1989)]. We now have used three approaches to distinguish the nonadrenergic [3H]idazoxan sites from alpha 2-adrenergic receptors. (a) No nonadrenergic [3H]idazoxan binding sites were found in COS-7 cells transfected with the genes for the two known alpha 2-adrenergic receptor subtypes. (b) The ratio of alpha 2-adrenergic and nonadrenergic [3H]idazoxan sites in human platelet membranes varied considerably between various donors. (c) Highly purified platelet plasma membranes were enriched for alpha 2-adrenergic receptors but did not contain any nonadrenergic [3H]idazoxan binding sites. We conclude that the nonadrenergic [3H]idazoxan binding sites are not co-expressed with alpha 2-adrenergic receptors and at least in human platelets may be located in an intracellular compartment.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Michel MC,Regan JW,Gerhardt MA,Neubig RR,Insel PA,Motulsky HJsubject
Has Abstractpub_date
1990-01-01 00:00:00pages
65-8issue
1eissn
0026-895Xissn
1521-0111journal_volume
37pub_type
杂志文章abstract：:Neuroactive steroids have been postulated to cause anesthesia by binding to unique steroid recognition sites on gamma-aminobutyric acid (GABA) receptors and modulating GABA receptor function. Steroids interact with these sites diastereoselectively, but it is unknown whether steroid sites show enantioselectivity. To ad...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are recognized as the principal nicotine binding site in brain. Recombinant alpha4beta2 nAChR demonstrate biphasic concentration-response relationships with low- and high-EC50 components. This study shows that untranslated regions (UTR) can influence expression of...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.020198
更新日期：2006-07-01 00:00:00
abstract：:We examined the role of putative trafficking sequences in two GABA(A) receptor subunits: α4 and δ. These subunits assemble with a β subunit to form a subtype of GABA(A) receptor involved in generating the "tonic" outward current. Both α4 and δ subunits contain dibasic retention motifs in homologous positions. When bas...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.092791
更新日期：2014-07-01 00:00:00
abstract：:We studied the mechanism by which the peptide omega-grammotoxin-SIA inhibits voltage-dependent calcium channels. Grammotoxin at concentrations of > 50 nM completely inhibited inward current carried by 2 mM barium through P-type channels in rat cerebellar Purkinje neurons when current was elicited by depolarizations up...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.6.1095
更新日期：1997-12-01 00:00:00
abstract：:Labeled histidine was taken up into rat leukemic basophil 2H3 cells by a system with high affinity for histidine and then decarboxylated to form histamine. Uptake was partially inhibited and decarboxylation was completely blocked by alpha-fluoromethylhistidine (alpha-FMH) at concentrations of 10-100 microM. alpha-FMH ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-08-01 00:00:00
abstract：:The intracellular pathways taken by galactose-terminal glycoproteins were examined following endocytosis by the asialoglycoprotein receptor in monolayers of the human hepatoma cell line, Hep G2. In addition to a pathway leading to lysosomal degradation, single cohort kinetics revealed that up to 28% of surface-bound a...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:We reported earlier that delta 9-tetrahydrocannabinol (THC), the main psychoactive ingredient in marihuana, increased markedly the level of unesterified arachidonic acid (AA) in guinea pig cerebral cortex slices prelabeled with [14C]AA. The purpose of the present study was to clarify the mechanism underlying THC-enhan...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:Interleukin 6 (IL-6), which is elevated in patients with congestive heart failure and acts as both a chronic marker of inflammation and an acute-phase reactant, is associated with myocardial damage. Circulating levels of arginine vasopressin (AVP) are elevated during cardiac stress and could be a factor for cardiac in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107698
更新日期：2017-09-01 00:00:00
abstract：:Retina from 1-day-old chicks is a valuable tissue model for studying neuronal nicotinic receptors because it expresses a large number of the developmentally regulated high affinity [(3)H]epibatidine labeled nicotinic receptors. Most of these receptors contain the beta4 subunit associated with different alpha subunits....
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.6.1410
更新日期：2001-06-01 00:00:00
abstract：:Atropine, the classic muscarinic receptor antagonist, inhibits ion currents mediated by neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes. At the holding potential of -80 mV, 1 microM atropine inhibits 1 mM acetylcholine-induced inward currents mediated by rat alpha2beta2, alpha2beta4, alp...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.5.886
更新日期：1997-11-01 00:00:00
abstract：:Arrestins mediate G protein-coupled receptor desensitization, internalization, and signaling. Dopamine D(2) and D(3) receptors have similar structures but distinct characteristics of interaction with arrestins. The goals of this study were to compare arrestin-binding determinants in D(2) and D(3) receptors other than ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.050534
更新日期：2009-01-01 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：:PC-12 cells, derived from a rat pheochromocytoma, were found to take up tritiated serotonin ([3H]5-HT) from the external medium by means of a saturable mechanism which follows Michaelis-Menten kinetics. The apparent Km of uptake was 0.39 microM and the Vmax was 0.40 pmole/min/10(6) cells. The uptake was temperature-de...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:Previous studies revealed that phenylhistamines and histaprodifens possess higher potency and affinity at guinea pig histamine H(1)-receptor (gpH(1)R) than at human histamine H(1)-receptor (hH(1)R). However, we recently identified an imidazolylpropylguanidine [N(1)-(3-cyclohexylbutanoyl)-N(2)-[3-(1H-imidazol-4-yl)-pro...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.053009
更新日期：2009-03-01 00:00:00
abstract：:The anticancer agent 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its methyl ester (CDDO-Me) typically induce a broad spectrum of growth-inhibitory, proapoptotic, and antiangiogenic responses. Treatment of Panc1, Panc28, and L3.6pL pancreatic cancer cells with low micromolar concentrations of CDDO or CDDO-...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.064451
更新日期：2010-08-01 00:00:00
abstract：:The carbonic anhydrase (CA) isozyme (IV) in microsomes is thought to have a dominant role in secretory processes. Using microsomes from bovine kidney and lung (which had the same activity), we have measured the Km and kcat for CO2 hydration and compared these numbers with those for CA I (red blood cells and gut), CA I...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-10-01 00:00:00
abstract：:Bovine adrenal zona fasciculata (AZF) cells express a noninactivating K+ current (IAC) that sets the resting membrane potential and may mediate depolarization-dependent cortisol secretion. External ATP stimulates cortisol secretion through activation of a nucleotide receptor. In whole-cell patch clamp recordings from ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.55.2.364
更新日期：1999-02-01 00:00:00
abstract：:4-PIOL is a structural analog of GABA that has low efficacy at GABAA receptor CI- channels and activates a nondesensitizing CI- conductance in central neurons. We investigated the biophysical mechanisms of its low efficacy in embryonic olfactory bulb neurons, which express a limited number of GABAA receptor subunit tr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:4-Methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz), a prototype drug candidate containing a 1,2-dithiole-3-thione moiety, has been widely studied as a cancer chemopreventive agent. Oltipraz and other novel 1,2-dithiole-3-thione congeners have the capability to prevent insulin resistance via AMP-activated protei...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.051128
更新日期：2009-01-01 00:00:00
abstract：:The human caudate and putamen contain two high affinity binding sites for [3H]spiroperidol. Both of these affinity states exhibit dopaminergic selectivity. Ascorbic acid, at 0.1 mM, induces a slow loss of the low affinity component of [3H]spiroperidol binding in these tissues. The addition of guanyl nucleotides to the...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:Valproic acid (VPA) is an effective antiepileptic drug with an additional activity for the treatment of bipolar disorder. It has been assumed that both activities arise from a common target. At the molecular level, VPA targets a number of distinct proteins that are involved in signal transduction. VPA inhibition of in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.030601
更新日期：2007-03-01 00:00:00
abstract：:The interaction of quinidine with a cloned human cardiac potassium channel (HK2) expressed in a stable mouse L cell line was studied using the whole-cell tight-seal voltage-clamp technique. Quinidine (20 microM) did not affect the initial sigmoidal activation time course of the current. However, it reduced the peak cu...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-02-01 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：:The binding kinetics of [3H]Ro 15-1788, a selective benzodiazepine receptor antagonist, to synaptosomal membranes of rat cerebral cortices was studied. [3H]Ro 15-1788 binds with high affinity (dissociation constant, 0.53 nM) to a single class of binding sites (maximal binding capacity, 1.97 pmoles/mg of protein). Equi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:In previous studies, we have shown that mouse RAW 264.7 macrophages possess pyrimidinoceptors, coupled to a phosphoinositide-specific phospholipase C, with a higher specificity for UTP than for ATP. In the current study, we explored the mechanism involved in the UTP-induced intracellular acidification seen in this cel...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.53.2.313
更新日期：1998-02-01 00:00:00
abstract：:Thrombin, the key effector protease of the coagulation cascade, drives fibrin deposition and activates human platelets through protease-activated receptor-1 (PAR1). These processes are critical to the progression of thrombotic diseases. Thrombin is the main target of anticoagulant therapy, and major efforts have led t...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.096446
更新日期：2015-07-01 00:00:00
abstract：:The metabotropic glutamate 5 receptor and the cannabinoid type 1 receptor are G protein-coupled receptors that are widely expressed in the central nervous system. Metabotropic glutamate 5 receptors, present at the postsynaptic site, are coupled to Gαq/11 proteins and display an excitatory response upon activation, whe...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.116.104372
更新日期：2016-11-01 00:00:00
abstract：:Herpes simplex virus type 1 (HSV-1) encodes a thymidine kinase (TK) that markedly differs from mammalian nucleoside kinases in terms of substrate specificity. It recognizes both pyrimidine 2'-deoxynucleosides and a variety of purine nucleoside analogs. Based on a computer modeling study and in an attempt to modify thi...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.6.1326
更新日期：2000-12-01 00:00:00
abstract：:In vivo administration of the porphyrogenic agent allylisopropylacetamide (AIA) to phenobarbital-pretreated rats results in marked loss of hepatic cytochrome P-450 content. Using isozyme-selective functional markers, we now show that such loss reflects inactivation of several phenobarbital-inducible and constitutive i...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
abstract：:Although much has been learned about the mechanisms of ligand selectivity between different opioid receptor subtypes, little is known about the common opioid binding pocket shared by all opioid receptors. The recently discovered orphanin system offers a good opportunity to study the mechanisms involved in the binding ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.53.4.772
更新日期：1998-04-01 00:00:00
