Increased expression of mu opioid receptors in animals susceptible to diet-induced obesity

Stimulation of mu opioid receptors preferentially increases the intake of a high fat diet. In this paper we investigated whether there was a difference in the expression of mu opioid receptors between animals susceptible (Osborne–Mendel) or resistant (S5B/Pl) to obesity induced by eating a high fat diet. Immunohistochemical studies demonstrated that Osborne–Mendel rats eating a chow diet had an increased number of mu opioid receptors in the arcuate nucleus when compared to S5B/Pl rats. These immunohistochemical findings were supported by Real Time-PCR which demonstrated that the mRNA level of mu opioid receptors was also increased in the hypothalamus of Osborne–Mendel rats compared to S5B/Pl rats. Low doses of the mu opioid receptor agonist DAMGO [d-Ala²-N-Me-Phe⁴-Glycol⁵]-enkephalin administered to Osborne–Mendel rats caused a significant increase in the preference for a diet high in fat. The same doses of DAMGO switched the diet preference of S5B/Pl rats to high fat but did not significantly increase food intake. The combination of these findings suggests that the increased levels of hypothalamic mu opioid receptors in Osborne–Mendel rats may contribute to their preference for a diet high in fat and increase their susceptibility to becoming obese.     

Sex differences in opioid analgesia, hyperalgesia, tolerance and withdrawal: Central mechanisms of action and roles of gonadal hormones

This article reviews sex differences in opiate analgesic and related processes as part of a Special Issue in Hormones and Behavior. The research findings on sex differences are organized in the following manner: (a) systemic opioid analgesia across mu, delta and kappa opioid receptor subtypes and drug efficacy at their respective receptors, (b) effects of the activational and organizational roles of gonadal steroid hormones and estrus phase on systemic analgesic responses, (c) sex differences in spinal opioid analgesia, (d) sex differences in supraspinal opioid analgesia and gonadal hormone effects, (e) the contribution of genetic variance to analgesic sex differences, (f) sex differences in opioid-induced hyperalgesia, (g) sex differences in tolerance and withdrawal-dependence effects, and (h) implications for clinical therapies.     

毛乌素沙地群落动态中克隆和非克隆植物作用的比较

毛乌素沙地的克隆植物适应当地的沙化环境 ,并对沙化景观具有积极的改造作用。对克隆植物群落和非克隆植物群落内裸地斑块植物入侵的野外对比观测实验表明 ,克隆植物群落内裸地斑块入侵植物所占的格子数显著地大于非克隆植物群落 ,克隆植物可以提高沙化景观的自我恢复能力 ,在沙化景观的恢复重建中是一种值得利用的生物资源。     

Clonal integration and its ecological significance in Hedysarum laeve, a rhizomatous shrub in Mu Us Sandland

Hedysarum laeve, a rhizomatous clonal half-shrub, commonly dominates in inland dunes in semiarid areas of northern China. This species propagates vegetatively by the extension of horizontal rhizomes resulting in programmed reiteration of apical and/or axillary meristems. In this study, ¹⁴C labeling and experimental defoliation were employed to test the photosynthate translocation within the interconnected parent–daughter ramet pairs. A proportion of ¹⁴C-photosynthates was transported from the parent ramet into the daughter ramet, the roots of the daughter ramet, and the rhizome; these three components showed more than 70% sink activity after 24-h translocation. On the other hand, the basipetal translocation (from daughter ramet into parent ramet) was relatively small with sink activity of less than 5%, but sink activity of the rhizome exceeded 10%. Defoliation had an influence on the photosynthate translocation between parent and daughter ramets. The intact parent ramets significantly increased their ¹⁴C-photosynthate translocation into defoliated daughter ramets when compared to intact daughter ramets. The daughter ramets transported significantly more ¹⁴C-photosynthates to the defoliated parent ramets than to the intact parent ramets. A portion of ¹⁴C-photosynthates was transported into the rhizome from both parent and daughter ramets, indicating that the rhizome is supported by both ramets for photosynthates. The clonal integration between ramets of the species through rhizome connection may confer benefit both to the ramets and the genet in adverse environments. Received: April 12, 2001 / Accepted: November 26, 2001     

猪Mu阿片受体基因外显子Ⅲ单核苷酸多态性

行为规癖 (古板行为 )是母猪一种常见的异常行为 ,表现为重复、不变化的行为模式 ,并且不带有明显的目的性。Mu阿片受体 (Muopioidreceptor,简称MOR)属于G蛋白偶联受体 ,分布在痛觉传导区以及与情绪和行为有关的区域 ,影响动物的神经反应和行为表现。本研究以Mu阿片受体基因作为候选基因 ,探讨影响母猪规癖性状的可能性。根据Mu阿片受体基因外显子Ⅲ的序列设计引物 ,用PCR -SSCP的方法对大白猪、长白猪和杜洛克猪进行单核苷酸多态性分析 ,发现该位点存在多态性。对两种纯合子片段克隆并测序表明 ,mRNA第 1169处存在C→T的单碱基突变 ,在第 12 2 6处存在C→A的单碱基突变 ,均为沉默突变。统计结果发现 3种基因型 (AA ,AB ,BB)在各品种中的分布不一致 ,χ2 独立性检验差异极显著 (P <0 0 1)。将大白猪 3种基因型同行为规癖性状进行最小二乘分析 ,结果表明 ,BB基因型与其他 2种基因型相比有较高的无食咀嚼表现频率 ,同AA型比较差异极显著 (P <0 0 1) ,咬栏和站立基因型间差异不显著。因此 ,推测Mu阿片受体基因可能是影响母猪无食咀嚼性状的主效基因或与控制该性状的主效基因连锁     

浑善达克退化沙地恢复演替18年中植物群落动态变化

探讨了浑善达克退化沙地草地围封后流动沙丘的稳定程度 ,以及相应的群落特征随恢复进程的变化规律。采用空间序列代替时间序列的方法 ,从物种丰富度、生活型及功能型多样性等方面探讨了围封 18a(1985～ 2 0 0 3年 )过程中草地自然恢复演替进程。在这一过程中 ,物种多样性、丰富度和生物量随恢复演替先增加而后基本稳定或略有降低 ,呈抛物线型的变化趋势 (P<0 .0 0 1)。依群落特征变化 ,大致可将退化沙地恢复过程分为 3个阶段 :(1)流动沙丘向半固定沙丘转变的过程。在围封的前 2 a内 ,群落盖度增加 6倍 ,物种丰富度增加了 1倍 ,而物种多样性增加较缓慢 ;(2 )半固定沙丘向固定沙丘演替的过程。围封后 3～5 a内 ,尽管群落盖度只增加了约 2 0 % ,但物种丰富度和多样性显著增加 ,植物种类在 3a期间增加了 15种 ,是沙地恢复演替的关键时期 ;(3)固定沙丘稳定阶段。围封第 6 a后 ,群落总盖度、生物多样性、物种丰富度保持不变或略呈下降趋势。在恢复演替中 ,C4 植物在初期起先锋作用 ;而 C3植物在后期对群落稳定起重要作用 ;豆科植物尽管在群落中所占的比重较小 ,但可能对改善沙丘土壤养分方面起重要作用。从生活型多样性来看 ,1年生植物在恢复演替早期阶段对沙丘稳固起重要作用 ;而中后期群落则以多年生植物为     

浑善达克沙地四种生境中榆树天然更新幼苗发育的比较

对浑善达克沙地腹地风蚀低地、覆沙草地、平坦流动沙地和流动沙丘阴坡 4种类型生境中植物群落和榆树幼苗生长的比较研究结果表明 :(1)尽管单个样方内植物种数生境间没有差异 ,但群落总盖度覆沙草地的最低 ,流动沙丘阴坡上的居中 ,风蚀低地和流沙平地的最高。榆树幼苗的分盖度风蚀低地的最高 ,在流沙平地的次之 ,在覆沙草地的最低 ,流动沙丘阴坡的介于流沙平地和覆沙草地的中间 ,但与二者没有显著性差异 ;(2 )风蚀低洼地的幼苗生长的最好 ,平均高度、主根长度、叶片数和叶面积均显著大于生长在覆沙草地和流沙平地的幼苗的。生长在流动沙丘阴坡上幼苗的植株高度、叶片数目和叶面积介于它们之间 ,主根长度与风蚀低地的没有显著差异 ;(3)风蚀低洼地榆树幼苗根、茎、叶各部分生物量都明显地高于生长在其它 3种生境中幼苗的 ,流动沙丘阴坡上榆树幼苗的生物量还明显高于生长在覆沙草地和流沙平地上的 ,生长在覆沙草地和流沙平地的榆树幼苗的生物量基本上没有差异。该结果说明 ,榆树幼苗在风蚀低地生长最好 ,其次是在流动沙丘阴坡 ,这两种生境可能是浑善达克沙地榆树更新的主要地方。     

猪Mu阿片受体基因单核苷酸多态性分析

Mu阿片受体（简称MOR）属于G蛋白藕联受体,分布在痛觉传导区,以及与情绪和行为有关的区域,影响动物的神经反应和行为表现。该研究以长白猪、大白猪和杜洛克猪为试验材料, 用8对引物对Mu阿片受体基因的5′ UTR区域、整个编码区和3′ UTR区域用PCR-SSCP方法进行了扫描,发现5处突变基因座（GenBank登录号：AF521309）。统计结果发现基因型频率分布与品种有关,大白猪突变基因型频率显著高于长白和杜洛克,本研究推测分布上的差异可能是由于长期的选择压力造成的。 Abstract:Mu opioid receptor (MOR) is a member of G protein-coupled receptor family,distributed in the pain transduction region in the brain and related to emotion and behaviour.This study was designed to investigate the Single Nucleotide Polymorphism (SNP) of Mu opioid receptor gene in various breeds,including duroc,landrace and Yorkshire.5′ UTR ( untranslate region),coding region and 3′ UTR of Mu opioid receptor gene were amplified by eight pairs of primers,and the Single Nucleotide Polymorphism (SNP) were detected by SSCP.Five polymorphisms were found (Genebank Accession number:AF521309).The results of χ2 test showed that the frequencies of genotypes in different breeds were significantly different (P＜0.01).The frequencies of mutation genotypes in Yorkshire were significantly higher than Duroc and Landrace.According to the above results,we can speculate the difference of the frequencies of genotypes may be the results of long term choice pressure.     

In Vivo Characterization of (−)(−)MCL-144 and (+)(−)MCL-193: Isomeric,Bivalent Ligands with Mu/Kappa Agonist Properties

Once opioid receptor dimers were postulated, a goal has been to synthesize and screen novel opioids, with the hope of furthering our knowledge of the structure-activity relationship of opioid ligands with the opioid receptors. The aim of the current study was to address whether two isomeric bivalent ligands would have pharmacological differences after central administration, in vivo. The two compounds, (−) bis(N-cyclobutylmethyl-morphinan-3-yl) sebacoylate dihydrochloride (MCL-144) and 1−((+)N-cyclobutylmethylmorphinan-3-yl)-10-((−) N-cyclobutylmethylmorphinan-3-yl)sebacolyate (MCL-193) are each linked by a 10-carbon chain ester. The active (−) enantiomer for both ligands is 3-hydroxy-N-cyclobutylmethyl morphinan ((−)MCL-101), a N-cyclobutylmethyl analogue of cyclorphan (J Med Chem 43:114–122, 2000). MCL-144 contains two active levo rotatory (−)(−) pharmacophores, while MCL-193 contains one active (−) and one inactive (+) pharmacophore of MCL-101. In vitro analysis demonstrated that all three compounds, (−)(−)MCL-144, (+)(−)MCL-193 and (−)MCL-101 were κ agonists and μ partial agonists. (−)(−)MCL-144 and (−)MCL-101 had much higher affinity for both the μ and κ opioid receptors compared to (+)(−)MCL-193. In vivo, (−)(−)MCL-144 and (+)(−)MCL-193 produced full dose–response curves, in the 55°C tail-flick test, with each compound having an ED₅₀ value of 3.0 nmol after intracerebroventricular (i.c.v.) administration. The analgesic properties of both compounds were antagonized by the μ-selective antagonist, β-funaltrexamine and the κ-selective antagonist nor-binaltorphimine. Concomitant, i.c.v., administration of either (−)(−)MCL-144 or (+)(−)MCL-193 with morphine, did not significantly antagonize morphine-induced antinociception at any dose tested. In antinociceptive tests, (−)(−)MCL-144 and (+)(−)MCL-193 had the same pharmacological properties, demonstrating that having two active pharmacophores separated by a 10-carbon spacer group did not increase the antinociceptive efficacy of the compound. Additionally, it was also of interest to compare (−)(−)MCL-145 and (−)(−)MCL-144, as the only difference between these bivalent ligands is the spacer region connecting the two pharmacophores, yet (−)(−)MCL-145 produced an ED₅₀ value 10-fold lower than (−)(−)MCL-144 (ED₅₀ values = 0.3 nmol and 3.0 nmol, respectively). Special issue article in honor of Dr. Ji-Sheng Han.     

Domain III function of Mu transposase analysed by directed placement of subunits within the transpososome

Assembly of the functional tetrameric form of Mu transposase (MuA protein) at the two att ends of Mu depends on interaction of MuA with multiple att and enhancer sites on supercoiled DNA, and is stimulated by MuB protein. The N-terminal domain I of MuA harbours distinct regions for interaction with the att ends and enhancer; the C-terminal domain III contains separate regions essential for tetramer assembly and interaction with MuB protein (IIIα and IIIβ, respectively). Although the central domain II (the ‘DDE’ domain) of MuA harbours the known catalytic DDE residues, a 26 amino acid peptide within IIIα also has a non-specific DNA binding and nuclease activity which has been implicated in catalysis. One model proposes that active sites for Mu transposition are assembled by sharing structural/catalytic residues between domains II and III present on separate MuA monomers within the MuA tetramer. We have used substrates with altered att sites and mixtures of MuA proteins with either wild-type or altered att DNA binding specificities, to create tetrameric arrangements wherein specific MuA subunits are nonfunctional in II, IIIα or IIIβ domains. From the ability of these oriented tetramers to carry out DNA cleavage and strand transfer we conclude that domain IIIα or IIIβ function is not unique to a specific subunit within the tetramer, indicative of a structural rather than a catalytic function for domain III in Mu transposition.