孤啡肽——新发现的内阿片肽及其受体

孤啡肽是最近发现的一个１７肽,其结构与已知的内阿片肽,尤其是强啡肽Ａ类似;但具有明显不同的药理学特性;与经典的阿片受体结合能力很弱,而与阿片受体家族中的一个新成员－－“孤儿受体”结合能力很强,因而认为是该受体的天然配基,孤啡肽脑室注射可使小鼠痛觉过敏,运动减少。孤啡肽受体是阿片受体家族中的新成员,属于Ｇ蛋白偶联受体,与经典的阿片受体配基亲和力均很弱,该受体激活后介导对腺苷酸环化酶活力的抑制。     

δ阿片肽受体分子药理学

目前已成功地克隆出δ、μ、κ阿片受体 ,均属Ｇ蛋白偶联受体 ,有 6 5 %同源序列 ,仅 35 %序列决定其特异性。阿片受体最大的同源区是跨膜区 (ｔｒａｎｓｍｅｍｂｒａｎｅ ,ＴＭ)和细胞内环 ,变化最大的区域在细胞外环及其氨基、羧基末端。近年来应用反义核酸技术、基因剔除、构建嵌合受体、基因定位突变、截短或缺失氨基酸突变等方法对阿片受体的结构和功能的研究取得了新进展。1 .内源性与克隆δ阿片受体δ阿片受体广泛分布于脑内 ,但在不同的脑区其分布密度不同。体内药理学实验证明 ,δ阿片受体有两种亚型δ1和δ2 [1] ,但是其亚型没被…     

阿片样物质与心脏缺血预处理

阿片肽和外源性阿片术物质如吗啡除了能缓解心肌梗塞造成的疼痛外,还具有减小梗塞范围和降低心律失常的发生等重要作用。心脏阿片受体参与了缺血预处理（IPC）对心脏的调节作用,阿片样物质激活心脏阿片受体还可模拟IPC对心脏的作用。心脏阿片受体的激活产生的急性即第一窗口期和延迟即第二窗口期的心脏保护作用的信号途径,与IPC相似,其信号通路涉及Gi/Go蛋白、蛋白激酶C、酪氨酸激酶和ATP敏感K^ 通道等途径。     

阿片成瘾机制研究进展及治疗展望

关于阿片类药物成瘾机制的研究是药物成瘾研究中的一个热点,本文从参与阿片成瘾的神经递质系统及其相互作用、不同阿片受体在成瘾过程中的作用、学习记忆与阿片成瘾的关系、成瘾性药物的细胞内信号转导机制等几个方面介绍了近年来的研究进展,并对阿片类药物成瘾治疗和预防和新方法进行了展望。     

κ-阿片肽在低氧性肺动脉高压形成中的作用

低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)是慢性阻塞性肺病、慢性高原病和新生儿肺病等临床众多心、肺疾病发病的重要的生理环节,其形成机制尚不完全清楚,防治也不十分理想.低氧性肺血管收缩反应(hypoxic pulmonary vaso-constriction,HPV)和肺血管结构重建(pulmonary artery remodeling,PAR)是HPH的两个主要发病环节,而肺动脉平滑肌细胞(pul-monary arterial smooth muscle cell,PASMC)内的钙稳态及膜离子通道,尤其是钙通道和钾通道活性的改变在其中又发挥了非常重要的作用.近年来关于κ-阿片肽对HPH的影响机制有一些研究.本文就其研究进展作一综述.     

阿片肽对胰岛素释放的影响

阿片肽作为一类重要的神经活性物质发挥着许多生物学效应,近来已有研究证明类阿片物质有影响胰岛素释放的作用.胰岛素是由胰岛β细胞分泌的一种重要激素,它可以调节机体的血糖稳定.因此这些结果将可能为糖尿病治疗开辟新天地,但其具体作用机制目前尚不清楚.本文根据国内外研究成果及最新研究进展,主要介绍了阿片肽及其受体的生理功能,阿片受体介导的信号转导以及阿片肽对胰岛素释放的调节机制.     

“内吗啡肽”的发现是阿片肽研究的一次突破

早在７０年代,人们即发现了内源性的δ阿片受体选择性配体（脑啡肽）和ｋ阿片受体选择性配体（强啡肽）,但一直未能找到内源性的μ阿片受体的选择性配体。１９９７年４月英国出版的“自然”杂志报道,发现了两种内源性的α阿片受体选择性配体,分别命名为ｅｎｄｏｍｏｒｐｈｉｎ－１（ＥＭ－１）和ｅｎｄｏｍｏｒｐｈｉｎ－２（ＥＭ－２）可译为“内吗啡肽”。本文拟就内吗啡肽的发现过程及其与其它内阿片肽的关系作一简要介绍。     

内源性阿片肽疼痛调节机制

内源性阿片肽(EOP)作为一类重要的神经递质发挥着许多生物学效应,而在痛觉信息的传递和调节过程中发挥的重要作用最为显著,这些结果将可能为疼痛治疗开辟新天地.本文就近年来EOP的研究进展,特别是关于它们在神经系统内的分布,组成,阿片受体的特点,疼痛调节的特点及其机制等方面作一综述.     

淋巴细胞存在有δ阿片肽受体的分子证据

以小鼠的成神经细胞瘤和大鼠神经胶质瘤的杂交细胞δ阿片肽受体的基因外显子Ⅲ序列为依据合成引物,应用ＲＴ－ＰＣＲ方法扩增人外周血淋巴细胞ｍＲＮＡ的一片段ｃＤＮＡ,扩增产物经纯化后进行核苷酸序列测定．测序结果表明该片段与杂交瘤细胞的δ阿片肽受体基因序列相比有５个同源区,其中碱基的同源性达６３％．实验结果从分子水平表明了人淋巴细胞表面存在有阿片肽受体的可能性．     

Opioid peptides

This review was presented as an overview at the meeting of the American Society for Pharmacology and Experimental Therapeutics in Portland, Oregon, in August, 1979. The intent of the talk was to briefly survey the current status of the field and to present some ideas as to future research. No attempt was made at an exhaustive review of the literature.     

Opioid peptides in man--analytical aspects

The opioid peptides present extraordinary problems for analysis, since they are structurally homologous yet substantially different. Within each of the three systems, proopiomelanocortin, proenkephalin and prodynorphin, a whole set of peptides of successively smaller sizes are generated. The biological relevance of the different peptides is not fully understood. Analytical strategies may either be specifically directed to individual peptide species or to identification of total system output.     

Opioid peptides in adrenal gland

Enkephalin-like immunoreactive peptides have been observed in adrenal glands of all species studied with the highest contents found in dogs and cows, and the lowest in rats. These peptides are located both in gland cells and in afferent nerve terminals. Bovine adrenal glands contain opioid peptides in many molecular forms. The peptides include a group of low molecular weight forms (M.W. <1000) which are capable of binding to the opiate receptor, and a group of high molecular weight forms (M.W. >1000) which contain enkephalin within their peptide sequence, but are devoid of opioid activity unless treated with trypsin. The physiological role(s) of the adrenal enkephalin-like material is not clear at present. However, it has been observed that nicotine-stimulated release of catecholamine from isolated chromaffin cells can be reduced by opiate agonists, suggesting that enkephalin-like peptide in nerve terminals may act on chromaffin cells. Several lines of evidence suggest that enkephalin-like peptides in gland cells can be released into the bloodstream.     

Opioid peptides as intercellular messengers

Opioid peptides are endogenous substances present in central nervous system and various tissues whose actions are mediated by opiate receptors. They belong to two different classes: short peptides like the two pentapeptides enkephalin and substances of higher molecular weight like beta-endorphin. It appears that these various peptides play a messenger role between cells, either as neurotransmitters in the case of enkephalins or as hormones in the case of beta-endorphin.     

Opioid peptides, regulators of acetylcholinesterase activity

Studies have been made on the opioid peptides--enkephalins their fragments, and alpha- and gamma-endorphins with concentrations of 10(-8)-10(-4) M, on acetylcholinesterase of human blood erythrocytes. It was found out that these peptides, which were fragments of one propeptide beta-LPH were reversible effectors of acetylcholinesterase. Enkephalins and a number of their fragments were noncompetitive inhibitors. It was shown that natural pentapeptide has the highest inhibitor activity; decreasing of inhibitor activity or the absence of it was a result of pentapeptide molecules degradation. Short endorphins were noncompetitive activators of acetylcholinesterase.