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1.
Both mu and delta opiate receptors exist on the same neuron 总被引：3，自引：0，他引：3
Low concentrations of the relatively selective opiate receptor agonists dihydromorphine and normorphine (mu receptor agonists) and D-Ala 2-D-Leu 5-enkephalin (a delta receptor agonist) were applied to single enteric neurons while the frequency of action potential firing was recorded. Most neurons that were inhibited by the mu agonists were also inhibited by the delta agonist, but the two receptors could be distinguished by the higher concentration of naloxone required to antagonize the delta agonist. The results indicate that enteric neurons bear both mu and delta receptors and that cell firing is inhibited if either receptor type is activated. 相似文献
2.
Exogenous cholecystokinin (CCK) decreases food intake and causes satiety in animals and man. However, it has not been established that endogenous CCK causes satiety or whether the response is mediated by peripheral-type (CCK-A) or brain-type (CCK-B) receptors. The development of potent and selective antagonists for CCK-A (MK-329) and CCK-B (L-365,260) receptors now allows these issues to be addressed. The CCK-A antagonist MK-329 and the CCK-B antagonist L-365,260 increased food intake in partially satiated rats and postponed the onset of satiety; however, L-365,260 was 100 times more potent than MK-329 in increasing feeding and preventing satiety. These results suggest that endogenous CCK causes satiety by an agonist action on CCK-B receptors in the brain. 相似文献
3.
Bohn LM Lefkowitz RJ Gainetdinov RR Peppel K Caron MG Lin FT 《Science (New York, N.Y.)》1999,286(5449):2495-2498
The ability of morphine to alleviate pain is mediated through a heterotrimeric guanine nucleotide binding protein (G protein)-coupled heptahelical receptor (GPCR), the mu opioid receptor (muOR). The efficiency of GPCR signaling is tightly regulated and ultimately limited by the coordinated phosphorylation of the receptors by specific GPCR kinases and the subsequent interaction of the phosphorylated receptors with beta-arrestin 1 and beta-arrestin 2. Functional deletion of the beta-arrestin 2 gene in mice resulted in remarkable potentiation and prolongation of the analgesic effect of morphine, suggesting that muOR desensitization was impaired. These results provide evidence in vivo for the physiological importance of beta-arrestin 2 in regulating the function of a specific GPCR, the muOR. Moreover, they suggest that inhibition of beta-arrestin 2 function might lead to enhanced analgesic effectiveness of morphine and provide potential new avenues for the study and treatment of pain, narcotic tolerance, and dependence. 相似文献
4.
Morphiceptin (NH4-tyr-pro-phe-pro-COHN2): a potent and specific agonist for morphine (mu) receptors 总被引：8，自引：0，他引：8
The synthetic peptide NH2-Tyr-Pro-Phe-Pro-CONH2 (morphiceptin), which is the amide of a fragment of the milk protein beta-casein, has morphinelike activities and is highly specific for morphine (mu) receptors but not for enkephalin (delta) receptors. It is as active as morphine in the guinea pig ileum but much less active in the mouse and rat vas deferens. The discovery of this specific morphine receptor ligand substantiates the hypothesis of multiple opiate receptors. The ligand, which may be of physiological significance since a very similar, or identical, activity can be detected in enzymatic digests of beta-casein, may prove useful for further investigation of the functions of opiate receptor subtypes. 相似文献
5.
Whistler JL Enquist J Marley A Fong J Gladher F Tsuruda P Murray SR Von Zastrow M 《Science (New York, N.Y.)》2002,297(5581):615-620
Recycling of the mu opioid receptor to the plasma membrane after endocytosis promotes rapid resensitization of signal transduction, whereas targeting of the delta opioid receptor (DOR) to lysosomes causes proteolytic down-regulation. We identified a protein that binds preferentially to the cytoplasmic tail of the DOR as a candidate heterotrimeric GTP-binding protein (G protein)-coupled receptor-associated sorting protein (GASP). Disruption of the DOR-GASP interaction through receptor mutation or overexpression of a dominant negative fragment of GASP inhibited receptor trafficking to lysosomes and promoted recycling. The GASP family of proteins may modulate lysosomal sorting and functional down-regulation of a variety of G protein-coupled receptors. 相似文献
6.
Naloxazone, a hydrazone derivative of the opiate antagonist naloxone, has a high affinity for opiate receptor binding sites. Naloxazone injections reduce opiate receptor binding to extensively washed mouse brain membranes for more than 24 hours, suggesting that the effect is irreversible. High-affinity binding sites are abolished by this treatment, whereas low-affinity sites are unaffected. Naloxazone treatment blocks the analgesic effects of morphine for at least 24 hours but does not prevent death from high doses of morphine. Thus analgesic but nonlethal opiate effects may be mediated by the high-affinity subpopulation of opiate receptors. 相似文献
7.
Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice 总被引：26，自引：0，他引：26
S L Hofmann D W Russell M S Brown J L Goldstein R E Hammer 《Science (New York, N.Y.)》1988,239(4845):1277-1281
A complementary DNA encoding the human low density lipoprotein (LDL) receptor under control of the mouse metallothionein-I promoter was injected into fertilized mouse eggs, and a strain of mice expressing high levels of LDL receptors was established. After administration of cadmium, these mice cleared intravenously injected 125I-labeled LDL from blood eight to ten times more rapidly than did normal mice. The plasma concentrations of apoproteins B-100 and E, the two ligands for the LDL receptor, declined by more than 90 percent after cadmium treatment, but the concentration of another apoprotein, A-I, was unaffected. Therefore, overexpression of an endocytotic receptor can dramatically lower the ambient concentration of its ligand in vivo. 相似文献
8.
Geller DS Farhi A Pinkerton N Fradley M Moritz M Spitzer A Meinke G Tsai FT Sigler PB Lifton RP 《Science (New York, N.Y.)》2000,289(5476):119-123
Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation. 相似文献
9.
A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. 总被引：79，自引：0，他引：79
S Higashiyama J A Abraham J Miller J C Fiddes M Klagsbrun 《Science (New York, N.Y.)》1991,251(4996):936-939
Macrophage-like U-937 cells secrete a 22-kilodalton heparin-binding growth factor that is mitogenic for BALB-3T3 fibroblasts and smooth muscle cells, but not endothelial cells. The amino acid sequence predicted from complementary DNA clones indicates that the mitogen is a new member of the epidermal growth factor (EGF) family. This heparin-binding EGF-like growth factor (HB-EGF) binds to EGF receptors on A-431 epidermoid carcinoma cells and smooth muscle cells, but is a far more potent mitogen for smooth muscle cells than is EGF. HB-EGF is also expressed in cultured human macrophages and may be involved in macrophage-mediated cellular proliferation. 相似文献
10.
Receptor binding of opiate agonists and antagonists can be differentiated in vivo and in vitro. Administration of either rapidly elevates stereospecific [(3)H]dihydromorphine binding to mouse brain extracts by 40 to 100 percent, but antagonists are 10 to 1000 times more potent than agonists; as little as 0.02 milligram of naloxone per kilogram of body weight significantly enhances opiate receptor binding. Sodium enhances antagonist binding in vitro but decreases agonist binding, a qualitative difference that may be relevant to the divergent pharmacological properties of opiate agonists and antagonists. 相似文献
11.
杨树苗圃使用草甘膦、百草枯化学除草试验 总被引：4，自引：0，他引：4
在杨树苗圃,使用草甘膦、百草枯进行化学除草试验的结果表明,除草效果均达90%以上。草甘膦的除草效果优于百草枯,草甘膦持效时间在60 d以上,百草枯为30 d以上,草甘膦以100 g/667 m2加水40 kg,百草枯以150 ml/667 m2加水40 kg使用效果为最佳。并且百草枯与拉索混用,除草效果更好。同人工除草相比,节省费用64~71%。 相似文献
12.
Mapping of heavy chain genes for mouse immunoglobulins M and D 总被引：50，自引：0，他引：50
13.
Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. 总被引：71，自引：0，他引：71
The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence. 相似文献
14.
Identification of a T3-associated gamma delta T cell receptor on Thy-1+ dendritic epidermal Cell lines 总被引：27，自引：0，他引：27
F Koning G Stingl W M Yokoyama H Yamada W L Maloy E Tschachler E M Shevach J E Coligan 《Science (New York, N.Y.)》1987,236(4803):834-837
The murine epidermis contains a subpopulation of bone marrow-derived lymphocytes that have a dendritic morphology and that express Thy-1 and T3 cell-surface antigens but not other markers (L3T4 or Lyt-2) characteristic of mature peripheral T lymphocytes. An alternative type of T cell receptor was earlier identified on a subpopulation of murine thymocytes with a similar phenotype (T3+, L3T4-, Lyt-2-), but not on peripheral murine T lymphocytes. Two independently derived Thy-1+, L3T4-, and Lyt-2- dendritic cell lines of epidermal origin that express a T3-associated disulfide-linked heterodimer composed of a 34-kilodalton gamma-chain and 46-kilodalton partner (the delta chain) have now been identified. Analysis of N-linked glycosylation revealed that this receptor is similar to that detected on thymocytes. These results demonstrate that Thy-1+ dendritic epidermal cell lines can express gamma delta T cell receptors in vitro and suggest that Thy-1+ dendritic epidermal cells express such receptors in vivo. The localization of these gamma delta T cell receptor-expressing cells in the epidermis may be of importance for understanding the function of these receptors. 相似文献
15.
Amphetamine: differentiation by d and l isomers of behavior involving brain norepinephrine or dopamine 总被引：4，自引：0，他引：4
d-Amphetamine is markedly more potent an inhibitor of catecholamine uptake by norepinephrine neurons in the brain than is 1-amphetamine, whereas the two isomers are equally active in inhibiting catecholamine uptake by the dopamine neurons of the corpus striatum. In behavioral studies, d-amphetamine is ten times as potent as 1-amphetamine in enhancing locomotor activity, while it is only twice as potent in eliciting a compulsive gnawing syndrome. This suggests that the locomotor stimulation induced by amphetamine involves central norepinephrine, while dopamine neurons play an important role in the induced compulsive gnawing behavior. Assessment of differential actions of d- and 1-amphetamine may be an efficient method to differentiate behaviors involving norepinephrine or dopamine in the brain. 相似文献
16.
P D Suzdak J R Glowa J N Crawley R D Schwartz P Skolnick S M Paul 《Science (New York, N.Y.)》1986,234(4781):1243-1247
Ethanol, at pharmacologically relevant concentrations of 20 to 100 mM, stimulates gamma-aminobutyric (GABA) receptor-mediated uptake of 36Cl-labeled chlorine into isolated brain vesicles. One drug that acts at GABA-benzodiazepine receptors, the imidazobenzodiazepine Ro15-4513, has been found to be a potent antagonist of ethanol-stimulated 36Cl- uptake into brain vesicles, but it fails to antagonize either pentobarbital- or muscimol-stimulated 36Cl- uptake. Pretreatment of rats with Ro15-4513 blocks the anticonflict activity of low doses of ethanol (but not pentobarbital) as well as the behavioral intoxication observed with higher doses of ethanol. The effects of Ro15-4513 in antagonizing ethanol-stimulated 36Cl- uptake and behavior are completely blocked by benzodiazepine receptor antagonists. However, other benzodiazepine receptor inverse agonists fail to antagonize the actions of ethanol in vitro or in vivo, suggesting a novel interaction of Ro15-4513 with the GABA receptor-coupled chloride ion channel complex. The identification of a selective benzodiazepine antagonist of ethanol-stimulated 36Cl- uptake in vitro that blocks the anxiolytic and intoxicating actions of ethanol suggests that many of the neuropharmacologic actions of ethanol may be mediated via central GABA receptors. 相似文献
17.
利用A-1B超轻型飞机喷洒白僵菌、溴氰菊酯防治马尾松毛虫 总被引：12，自引：1，他引：11
用A-1B超轻型飞机喷洒白僵菌纯孢子柴油乳剂,2.5％溴氰菊酯乳油1:100倍液防治马尾松毛虫,作业流量180ml/亩、喷幅30—40米,白僵菌纯孢子5g/亩、溴氰菊酯2ml/亩。经测试溴氰菊酯扩散比DR>0.67,平均雾滴直径127—173μm,白僵菌DR=0.62,平均雾滴直径约139μm,溴氰菊酯防治死亡率95.5％,白僵菌防治白僵率94.84％。防治费平均每亩1.89元。结果表明:在闽北马尾松毛虫的偶发性灾区,超轻型飞机是一种经济、有效、有发展前景的防治机械。 相似文献
18.
We have assessed the effects in normal control volunteers of 2,5-dimethoxy-4-methyl-amphetamine, the chemical present in the hallucinogenic drug STP, in two independent trials. In low doses, this compound produces a mild euphoria. Doses greater than 3 milligrams may cause pronounced hallucinogenic effects lasting about 8 hours and similar to those produced by hallucinogenic doses of lysergic acid diethylamide, mescaline, and psilocybin. 2,5-Dimethoxy-4-methyl-amphetamine, which is chemically related to mescaline and amphetamine, is about 100 times more potent as a hallucinogen than mescaline and only one-thirtieth as potent as lysergic acid diethylamide. Its psychological effects are not accentuated by chlorpromazine. 相似文献
19.
Single receptor units in the compound eye of the horseshoe crab were illuminated, and their impulse discharges were recorded without removing the eye from the animal. The receptors were spontaneously active in darkness and responded without saturation over a light intensity range of 10(10) to 1. When the eye was excised, the receptors did not discharge in darkness and had an intensity range of 10(5) to 1, as is usually found. Experiments show that these and other differences result from cutting off the blood supply to the eye when it is excised. In addition, the range and shape of the intensity characteristic suggest that more than one receptor mechanism encodes light intensity in this eye. 相似文献
20.
Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit 总被引：58，自引：0，他引：58
H Band F Hochstenbach J McLean S Hata M S Krangel M B Brenner 《Science (New York, N.Y.)》1987,238(4827):682-684
The T cell receptor (TCR) delta protein is expressed as part of a heterodimer with TCR gamma, in association with the CD3 polypeptides on a subset of functional peripheral blood T lymphocytes, thymocytes, and certain leukemic T cell lines. A monoclonal antibody directed against TCR delta was produced that binds specifically to the surface of several TCR gamma delta cell lines and immunoprecipitates the TCR gamma delta as a heterodimer from Triton X-100 detergent lysates and also immunoprecipitates the TCR delta subunit alone after chain separation. A candidate human TCR delta complementary DNA clone (IDP2 O-240/38), reported in a companion paper, was isolated by the subtractive library approach from a TCR gamma delta cell line. This complementary DNA clone was used to direct the synthesis of a polypeptide that is specifically recognized by the monoclonal antibody to TCR delta. This complementary DNA clone thus corresponds to the gene that encodes the TCR delta subunit. 相似文献