Abstract:
:We have measured the opioid receptor reserve in the guinea pig ileum myenteric plexus by means of the site-directed alkylating agent, beta-chlornaltrexamine. Treatment of the tissue with low (less than 10 nM) concentrations of beta-chlornaltrexamine caused a parallel shift of the log concentration-response curves for both normorphine and dynorphin A-(1-13). Analysis of the resulting curves indicated that the Kd values were 1.5 +/- 0.5 X 10(-6) and 10 +/- 4 X 10(-9), respectively. Using the naloxone Ke to distinguish between the mu and kappa receptors in this tissue, we found that the receptor selectivities of normorphine and dynorphin A-(1-13) were unchanged after a maximum parallel shift, thus demonstrating that there are both spare mu and spare kappa receptors present. The spare-receptor fraction for both receptor types was about 90%. In morphine-tolerant preparations (chronic pellet implantation), there was an apparent reduction in the fraction of spare mu receptors without any change in the apparent affinity of normorphine. Reduction in the spare receptor fraction does not necessarily imply reduction in the number of binding sites. We suggest that this reduction in receptor reserve is the basis of opioid tolerance, since the agonist concentration needed to produce a given effect is expected to increase as the receptor reserve decreases.
journal_name
Proc Natl Acad Sci U S Aauthors
Chavkin C,Goldstein Adoi
10.1073/pnas.81.22.7253subject
Has Abstractpub_date
1984-11-01 00:00:00pages
7253-7issue
22eissn
0027-8424issn
1091-6490journal_volume
81pub_type
杂志文章abstract::We investigated the defensive behavior of honeybees under controlled experimental conditions. During an attack on two identical targets, the spatial distribution of stings varied as a function of the total number of stings, evincing the classic "pitchfork bifurcation" phenomenon of nonlinear dynamics. The experimental...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.22.12611
更新日期:1999-10-26 00:00:00
abstract::DNA fragments encoding the mouse steroid 21-hydroxylase (C21 or Cyp21A1) gene are de novo methylated when introduced into the mouse adrenocortical tumor cell line Y1 by DNA-mediated gene transfer. Although CCGG sequences within the C21 gene are de novo methylated, CCGG sites within flanking vector sequences, other mam...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.18.6853
更新日期:1989-09-01 00:00:00
abstract::Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a "critical period" for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their inn...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1200705109
更新日期:2012-10-16 00:00:00
abstract::The nit-2 major nitrogen regulatory gene of Neurospora crassa turns on the expression of various unlinked structural genes that specify nitrogen-catabolic enzymes under nitrogen-limitation conditions. The nit-2 gene encodes a protein of 1036 amino acid residues with a single zinc finger and a downstream basic region t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.14.5331
更新日期:1990-07-01 00:00:00
abstract::A 978-base-pair gene that encodes thymidylate synthase (TS; 5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45) from Lactobacillus casei has been synthesized and inserted into Escherichia coli expression vectors. The DNA sequence contains 35 unique restriction sites that are located an average of 28 ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.2.633
更新日期:1990-01-01 00:00:00
abstract::The diversity of the T cell receptor (TCR) repertoire is limited, because of the processes of positive and negative T cell selection. To obtain T cells with specificities beyond the immune system's capacity, we have developed a strategy for retroviral TCR display. In this approach, a library of T cell variants is gene...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.26.14578
更新日期:2000-12-19 00:00:00
abstract::Six alternative hypotheses for the phylogenetic origin of Bilateria are evaluated by using complete 18S rRNA gene sequences for 52 taxa. These data suggest that there is little support for three of these hypotheses. Bilateria is not likely to be the sister group of Radiata or Ctenophora, nor is it likely that Bilateri...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.26.15458
更新日期:1998-12-22 00:00:00
abstract::By adapting to sustained stimuli, hair cells in the internal ear retain their sensitivity to minute transient displacements. Because one model for adaptation asserts that this process is mediated by a myosin isozyme, we reasoned that we should be able to arrest adaptation by interfering with myosin's ATPase cycle thou...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.7.2710
更新日期:1993-04-01 00:00:00
abstract::To clone the gene for the human Na+/H+ antiporter, we first constructed a stable mouse LTK- cell line (LAP1) lacking Na+/H+ antiport activity. Second, we devised a selective technique based on acid killing that specifically sorts out cells expressing low levels of Na+/H+ antiport activity from a population of antiport...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.24.9388
更新日期:1986-12-01 00:00:00
abstract::A single-nucleotide polymorphism in the human arylamine N-acetyltransferase 2 (Nat2) gene has recently been identified as associated with insulin resistance in humans. To understand the cellular and molecular mechanisms by which alterations in Nat2 activity might cause insulin resistance, we examined murine ortholog N...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1716990115
更新日期:2017-12-26 00:00:00
abstract::Lipopolysaccharide (LPS) is the major glycolipid that is present in the outer membranes (OMs) of most Gram-negative bacteria. LPS molecules are assembled with divalent metal cations in the outer leaflet of the OM to form an impervious layer that prevents toxic compounds from entering the cell. For most Gram-negative b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0912872107
更新日期:2010-03-23 00:00:00
abstract::The water channel aquaporin 1 (AQP1) and certain Rh-family members are permeable to CO(2) and NH(3). Here, we use changes in surface pH (pH(S)) to assess relative CO(2) vs. NH(3) permeability of Xenopus oocytes expressing members of the AQP or Rh family. Exposed to CO(2) or NH(3), AQP1 oocytes exhibit a greater maxima...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0813231106
更新日期:2009-03-31 00:00:00
abstract::Operant conditioning techniques were used to assess how gender and song familiarity affect song discrimination in adult zebra finches (Taeniopygia guttata). Twenty-five males and females, divided into five cohorts, were trained to discriminate between conspecific songs at different times of year. Males discriminating ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.4.1368
更新日期:1992-02-15 00:00:00
abstract::In cat retina, antisera directed against tyrosine hydroxylase (tyrosine 3-monooxygenase; EC 1.14.16.2) labeled three morphologically distinct classes of neurons; amacrine cells, displaced amacrine cells, and interplexiform cells. These three cell populations differed not only in their morphologies but also in their nu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.18.6335
更新日期:1985-09-01 00:00:00
abstract::Genome editing with engineered site-specific endonucleases involves nonhomologous end-joining, leading to reading frame disruption. The approach is applicable to dominant negative disorders, which can be treated simply by knocking out the mutant allele, while leaving the normal allele intact. We applied this strategy ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1512028113
更新日期:2016-05-17 00:00:00
abstract::Human infections with Ebola virus (EBOV) result in a deadly viral disease known as Ebola hemorrhagic fever. Up to 90% of infected patients die, and there is no available treatment or vaccine. The sporadic human outbreaks are believed to result when EBOV "jumps" from an infected animal to a person and is subsequently t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0809698105
更新日期:2008-11-18 00:00:00
abstract::Agrobacterium tumefaciens is routinely used to engineer desirable genes into dicotyledonous plants. However, the economically important graminaceous plant maize is refractory to tumor induction by inoculation with virulent strains of A. tumefaciens. Currently, the only clearcut evidence for transferred DNA (T-DNA) tra...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.4.1488
更新日期:1993-02-15 00:00:00
abstract::Nucleotide sequence analysis of one of several tRNA genes cloned from Tetrahymena thermophila macronuclear DNA indicated that it corresponds to a tRNA species having TTA as anticodon. Subsequently, the tRNA species corresponding to that gene was isolated and its nucleotide sequence was determined by post-labeling tech...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.14.4758
更新日期:1985-07-01 00:00:00
abstract::Replication of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) requires proteolytic processing of the replicase polyprotein by two viral cysteine proteases, a chymotrypsin-like protease (3CLpro) and a papain-like protease (PLpro). These proteases are important targets for development of antiviral drugs...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0510851103
更新日期:2006-04-11 00:00:00
abstract::The assembly of regional biotas and organismal responses to anthropogenic climate change both depend on the capacity of organisms to adapt to novel ecological conditions. Here we demonstrate the concept of evolutionary lag time, the time between when a climatic regime or habitat develops in a region and when it is col...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1308721110
更新日期:2013-07-09 00:00:00
abstract::Non-protein-coding RNA genes play an important role in various biological processes. How new RNA genes originated and whether this process is controlled by similar evolutionary mechanisms for the origin of protein-coding genes remains unclear. A young chimeric RNA gene that we term sphinx (spx) provides the first insi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.072066399
更新日期:2002-04-02 00:00:00
abstract::The S10 ribosomal protein operon is regulated autogenously by the product of one of the genes of the operon, the gene encoding ribosomal protein L4. We have used site-directed mutagenesis to isolate leader mutations affecting L4 control. The phenotypes of these mutants demonstrate that L4 regulates both transcription ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.18.6516
更新日期:1987-09-01 00:00:00
abstract::Surface topography profoundly influences cell adhesion, differentiation, and stem cell fate control. Numerous studies using a variety of materials demonstrate that nanoscale topographies change the intracellular organization of actin cytoskeleton and therefore a broad range of cellular dynamics in live cells. However,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1910166116
更新日期:2019-11-12 00:00:00
abstract::Apolipoprotein E (apoE) secreted by macrophages in the artery wall exerts an important protective effect against the development of atherosclerosis, presumably through its ability to promote lipid efflux. Previous studies have shown that increases in cellular free cholesterol levels stimulate apoE transcription in mac...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.021488798
更新日期:2001-01-16 00:00:00
abstract::The major protein constituent of human plasma high density lipoproteins has been isolated and its complete amino-acid sequence determined. The protein, designated apolipoprotein-glutamine-I by the presence of carboxyl-terminal glutamine, is a single polypeptide chain of 245 amino-acid residues, including three residue...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.9.3631
更新日期:1974-09-01 00:00:00
abstract::The mechanisms regulating clonal expansion and contraction of T cells in response to immunization remain to be identified. A recent study established that there was a log-linear relation between CD4 T-cell precursor number (PN) and factor of expansion (FE), with a slope of ∼-0.5 over a range of 3-30,000 precursors per...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1019706108
更新日期:2011-02-22 00:00:00
abstract::Recent research links diet-induced obesity (DIO) with impaired immunity, although the underlying mechanisms remain unclear. We find that the induction of inducible NO synthase (iNOS) and cytokines is suppressed in mice with DIO and in bone marrow macrophages (BMMPhi) from mice with DIO exposed to an oral pathogen, Por...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0904412106
更新日期:2009-06-30 00:00:00
abstract::Thioredoxin (Trx) is an intracellular redox protein with extracellular cytokine-like and chemokine-like activities. We show here that, although plasma Trx levels are unrelated to survival of HIV-infected individuals with CD4 cell counts above 200/microl blood, survival is significantly impaired (P = 0.003) when plasma...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.041624998
更新日期:2001-02-27 00:00:00
abstract::Identifying causal effects in nonexperimental data is an enduring challenge. One proposed solution that recently gained popularity is the idea to use genes as instrumental variables [i.e., Mendelian randomization (MR)]. However, this approach is problematic because many variables of interest are genetically correlated...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1707388115
更新日期:2018-05-29 00:00:00
abstract::The environmental backdrop to the evolution and spread of early Homo sapiens in East Africa is known mainly from isolated outcrops and distant marine sediment cores. Here we present results from new scientific drill cores from Lake Malawi, the first long and continuous, high-fidelity records of tropical climate change...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0703874104
更新日期:2007-10-16 00:00:00