Abstract：
:Intracellular recordings of membrane potassium current were made from rat locus coeruleus in vitro. The effects of agonists at mu-opioid receptors were studied on neurons from rats that had been chronically treated with morphine; these were compared with actions on neurons from control rats. Tolerance to the opioid-induced increase in potassium conductance was observed, and this was more pronounced for normorphine than for [Met5]enkephalin and [D-Ala2, Mephe4, Gly5-ol]enkephalin: experiments with the irreversible receptor blocker beta-chlornaltrexamine indicated that normorphine had lower intrinsic efficacy than [Met5]enkephalin and [D-Ala2 MePhe4, Gly5-ol]enkephalin. This adaptation was not due to any change of the properties of the potassium conductance activated by mu-receptors because both full and partial agonists at alpha 2-adrenoceptors, which couple to the same potassium conductance, were unchanged in their effectiveness; nor was it associated with any change in the affinity of mu-receptors for the antagonist naloxone. Naloxone had no effect on the neurons other than simple competitive reversal of the action of the mu-receptor agonists. These results demonstrate that 1) the mechanism responsible for tolerance in locus coeruleus neurons is specifically associated with mu-receptors and/or their coupling to potassium channels, 2) the intrinsic efficacy of an opioid determines the degree of tolerance observed, and 3) tolerance and physical dependence can be dissociated at the cellular level.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Christie MJ,Williams JT,North RAsubject
Has Abstractpub_date
1987-11-01 00:00:00pages
633-8issue
5eissn
0026-895Xissn
1521-0111journal_volume
32pub_type
杂志文章abstract：:Secreted R-spondin proteins (RSPOs1-4) function as adult stem cell growth factors by potentiating Wnt signaling. Simultaneous binding of distinct regions of the RSPO Fu1-Fu2 domain module to the extracellular domains (ECDs) of the LGR4 G protein-coupled receptor and the ZNRF3 transmembrane E3 ubiquitin ligase regulate...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.114.095133
更新日期：2015-01-01 00:00:00
abstract：:The transient receptor potential cation channel subfamily V member 1 (TRPV1) is known as a thermosensor and integrator of inflammation-induced hyperalgesia. TRPV1 is expressed in a subpopulation of primary afferent neurons that express several different neurotransmitters. The role of the TRPV1 channel in the developme...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.089532
更新日期：2014-02-01 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：:Recombinant interferon-alpha (IFN) enhances the cytotoxic effects of the fluorinated pyrimidine, 5-fluorouracil (5FU), against two human colon cancer cell lines. The aspartate transcarbamylase (ATCase) inhibitor, N-(phosphonacetyl)-L-aspartate (PALA), was studied in combination with 5FU/IFN to determine whether furthe...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-11-01 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：:Adenosine receptors of the A1 and A2 subtypes were characterized in membranes from DDT1 MF-2 smooth muscle cells. These cells possess a high density of A1 adenosine receptors (Bmax = 0.8-0.9 pmol/mg of protein), as measured by both agonist and antagonist radioligands. Agonists compete for [125I]N6-[2-(4-amino-3-iodoph...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-02-01 00:00:00
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：:Activation of muscarinic cholinergic receptors of 1321N1 human astrocytoma cells attenuates cyclic AMP accumulation. This effect results from an activation of phosphodiesterase with no direct inhibition of adenylate cyclase activity. In spite of this lack of coupling of muscarinic receptors to adenylate cyclase, guani...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-06-01 00:00:00
abstract：:The relationship between receptor number and agonist-induced intracellular responses has been well studied in receptors coupled to adenylate cyclase; however, for receptors coupled to phospholipase C (PLC), very little is known about the effect of receptor number on receptor-mediated processes. To explore this issue, ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.5.721
更新日期：1997-05-01 00:00:00
abstract：:G protein-coupled receptors are sensors that interact with a large variety of elements, including photons, ions, and large proteins. Not surprisingly, these receptors participate in the numerous normal physiologic processes that we refer to as health and in its perturbations that constitute disease. It has been estima...
journal_title：Molecular pharmacology
pub_type：
doi：10.1124/mol.116.106062
更新日期：2016-11-01 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：:Previous studies showed that lapatinib and obatoclax interact in a greater-than-additive fashion to cause cell death and do so through a toxic form of autophagy. The present studies sought to extend our analyses. Lapatinib and obatoclax killed multiple tumor cell types, and cells lacking phosphatase and tensin homolog...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.081539
更新日期：2012-12-01 00:00:00
abstract：:TNP-ATP has become widely recognized as a potent and selective P2X receptor antagonist, and is currently being used to discriminate between subtypes of P2X receptors in a variety of tissues. We have investigated the ability of TNP-ATP to inhibit alpha,beta-methylene ATP (alpha,beta-meATP)-evoked responses in 1321N1 hu...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.58.6.1502
更新日期：2000-12-01 00:00:00
abstract：:Understanding the structures of active and inactive agonist- and antagonist-bound receptor complexes is of great interest. In this work, we focus on position 30 of cholecystokinin (CCK) and its spatial approximation with the type A CCK receptor. For this, we developed two photoaffinity labeling probes, replacing the n...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.012179
更新日期：2005-06-01 00:00:00
abstract：:Intermediate-conductance (KCa3.1) and small-conductance (KCa2) calcium-activated K+ channels are gated by calcium binding to calmodulin (CaM) molecules associated with the calmodulin-binding domain (CaM-BD) of these channels. The existing KCa activators, such as naphtho[1,2-d]thiazol-2-ylamine (SKA-31), 6,7-dichloro-1...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.117.109421
更新日期：2017-10-01 00:00:00
abstract：:Ethylketocyclazocine (EKC) binds to two sites on NCB-20 neuroblastoma X Chinese hamster brain hybrid cells (KDH = 2 nM, Bmax = 21,000 sites/cell; KDL = 27 nM, Bmax = 140,000 sites/cell. The high-affinity site has been characterized as a delta opiate receptor. The low-affinity site is relatively benzomorphan-specific; ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:Very few antagonists have been identified for the human pregnane X receptor (PXR). These molecules may be of use for modulating the effects of therapeutic drugs, which are potent agonists for this receptor (e.g., some anticancer compounds and macrolide antibiotics), with subsequent effects on transcriptional regulatio...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.049437
更新日期：2008-09-01 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：:Immune-mediated drug hypersensitivity reactions (IDHRs) represent a significant problem due to their unpredictable and severe nature, as well as the lack of understanding of the pathogenesis. Sulfamethoxazole (SMX), a widely used antibiotic, has been used as a model compound to investigate the underlying mechanism of ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.107.043273
更新日期：2008-06-01 00:00:00
abstract：:15-Deoxy delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), an activator of peroxisome proliferator-activated receptor (PPAR)-gamma and -delta, is a prostanoid metabolite with anti-inflammatory actions. In intrauterine tissues, proinflammatory cytokines and prostaglandins have been identified as playing key roles in the ma...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.104.009449
更新日期：2005-07-01 00:00:00
abstract：:Upon sustained insult, kinins are released and many kinin responses, such as inflammatory pain, adapt from a B2 receptor (B2R) type in the acute phase to a B1 receptor (B1R) type in the chronic phase. In this study, we show that kinins modulate receptor endocytosis to rapidly decrease B2R and increase B1R on the cell ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.106.030858
更新日期：2007-02-01 00:00:00
abstract：:The chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) shows potent and selective anticancer and antimetastatic activity. However, the mechanism by which it is initially transported into cells to induce cytotoxicity is unknown. Hence, the current investigation examined the cellular uptake of ¹⁴C-Dp4...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.088393
更新日期：2013-12-01 00:00:00
abstract：:The subunit composition and pharmacological regulation of rat neuronal nicotinic cholinergic receptors were assessed. Specific immunoprecipitation was determined in solubilized rat brain homogenates using [3H]cytisine, a high affinity agonist at nicotinic receptors, in conjunction with polyclonal antisera generated ag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 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：:The X-ray structure of the bacterial sodium channel NavAb provides a new template for the study of sodium and calcium channels. Unlike potassium channels, NavAb contains P2 helices in the outer-pore region. Because the sequence similarity between eukaryotic and prokaryotic sodium channels in this region is poor, the s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.078212
更新日期：2012-07-01 00:00:00
abstract：:Studies were carried out to elucidate the mechanism whereby thyroid hormone (T3) induces NADPH:cytochrome P450 oxidoreductase (P450R) mRNA in rat liver in vivo. Northern blot analysis revealed that T3 treatment increases unspliced liver nuclear P450R RNA 4-fold within 8 h and that this induction precedes the induction...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.5.987
更新日期：2001-05-01 00:00:00
abstract：:Despite some blockbuster G protein-coupled receptor (GPCR) drugs, only a small fraction (∼ 15%) of the more than 390 nonodorant GPCRs have been successfully targeted by the pharmaceutical industry. One way that this issue might be addressed is via translation of recent deorphanization programs that have opened the pro...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.115.102301
更新日期：2016-03-01 00:00:00
abstract：:The ability of dopamine agonists and antagonists to compete with [3H]spiperone binding to rat striatal membrane preparations at 4, 15, 26, and 37 degrees varied markedly with temperature. Dopamine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN) were more potent at lower...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:The use of classic antipsychotic drugs is limited by the occurrence of extrapyramidal motor symptoms, which are caused by dopamine (DA) receptor blockade in the neostriatum. We examined the impact of early-life stress on haloperidol-induced catalepsy using the rat model of prenatal restraint stress (PRS). Adult "PRS r...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.113.085530
更新日期：2013-08-01 00:00:00
