Bitter peptides and bitter taste receptors

Bitter peptides are a structurally diverse group of oligopeptides often generated in fermented, aged, and hydrolyzed food products that make them unfavorable for consumption. Humans perceive bitterness by a repertoire of 25 human bitter receptors, termed T2Rs. Knowledge of the structural features of bitter receptors and of the factors that stimulate bitter receptors will aid in understanding the mechanism responsible for bitter taste perception. This article reviews the current knowledge regarding structural features of bitter peptides and bitter taste receptors. Received 24 November 2008; received after revision 11 December 2008; accepted 16 December 2008     

Snake venom components and their applications in biomedicine

Snake envenomation is a socio-medical problem of considerable magnitude. About 2.5 million people are bitten by snakes annually, more than 100,000 fatally. However, although bites can be deadly, snake venom is a natural biological resource that contains several components of potential therapeutic value. Venom has been used in the treatment of a variety of pathophysiological conditions in Ayurveda, homeopathy and folk medicine. With the advent of biotechnology, the efficacy of such treatments has been substantiated by purifying components of venom and delineating their therapeutic properties. This review will focus on certain snake venom components and their applications in health and disease. Received 6 July 2006; received after revision 14 August 2006; accepted 28 September 2006     

Liver X receptors in cardiovascular and metabolic disease

Liver X receptors (LXRs) α and β are nuclear oxysterol receptors and metabolic sensors initially found to regulate cholesterol metabolism and lipid biosynthesis. Recent studies have elucidated the importance of LXR in the development of cardiovascular diseases and metabolic disorders. LXR agonists prevent development of atherosclerosis by modulation of metabolic as well as inflammatory gene expression in rodent models. Moreover, LXR activation inhibits hepatic gluconeogenesis and lowers serum glucose levels, indicating possible application of LXR activation in the treatment of diabetes mellitus. However, first-generation LXR agonists elevate hepatic and serum trigylceride levels, making subtype-specific agonists and selective LXR modulators rather than unselective LXR agonists a potential pharmacological strategy. This review summarizes the multiple physiological and pathophysiological implications of LXRs and observations that identify LXRs as potential targets for therapeutic interventions in human cardiovascular and metabolic disease. Received 30 August 2005; received after revision 10 October 2005; accepted 4 November 2005     

Natural sweet macromolecules: how sweet proteins work

A few proteins, discovered mainly in tropical fruits, have a distinct sweet taste. These proteins have played an important role towards a molecular understanding of the mechanisms of taste. Owing to the huge difference in size, between most sweeteners and sweet proteins, it was believed that they must interact with a different receptor from that of small molecular weight sweeteners. Recent modelling studies have shown that the single sweet taste receptor has multiple active sites and that the mechanism of interaction of sweet proteins is intrinsically different from that of small sweeteners. Small molecular weight sweeteners occupy small receptor cavities inside two subdomains of the receptor, whereas sweet proteins can interact with the sweet receptor according to a mechanism called the ‘wedge model’ in which they bind to a large external cavity. This review describes these mechanisms and outlines a history of sweet proteins. Received 11 February 2006; received after revision 31 March 2006; accepted 11 May 2006     

EGFR基因C端结构域真核表达载体的构建

构建EGFR基因C端结构域的真核表达载体.应用PCR技术,从含EGFR基因C端结构域的大肠杆菌DH 5α中扩增其序列,亚克隆到真核表达载体pcDNA3.1( )中,经酶切及测序进行验证.PCR扩增片段与预期结果相符,真核表达载体构建成功,测序结果与GenBank公布的基因一致.成功地构建了EGFR基因C端两个结构域的真核表达载体.     

Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype

We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining a receptor displacement analysis, both opiate alkaloids displaced [³H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again suggesting that a novel mu opiate receptor may be present. Received 1 November 2001; received after revision 1 February 2002; accepted 1 February 2002     

外源性生长激素对改善腹腔感染时生长激素不敏感状态中的作用

探索了外源性生长激素对改善腹腔感染时生长激素不敏感中的作用。应用盲肠结扎穿孔法（CLP）制备腹腔感染大鼠模型,同时给予外源性生长激素;应用放射免疫法测定血清生长激素（GH）水平;应用逆转录多聚酶链反应（RT-PCR）法测定肝组织胰岛素样生长因子I(IGF-I)、生长激素受体（GHR）和细胞因子信号传导抑制体3(SOCS-3)mRNA的表达;应用ELISA测定血清肿瘤坏死因子α(TNF-α)和白介素6(IL-6)水平。结果表明腹腔感染组大鼠血清生长激素水平与对照组无明显差异,但肝组织IGF-ImRNA表达明显下降;给予外源性生长激素后可明显降低血清TNF-α和IL-6水平,同时可更快地促使GHR和IGF-ImRNA表达的上调及下调SOCS-3mRNA的表达。腹腔感染时机体存在对生长激素的不敏感状态,给予外源性生长激素后可明显地改善感染状态下机体对生长激素的敏感性。     

受体缺乏改变小鼠脑内组胺含量及昼夜节律

在乙谜麻醉下,分别于明时(8:00 a.m.)及暗时(8:00 p.m.)断头处死野生型及组胺H1R基因敲除型小鼠,迅速取出脑组织并分离出皮层、纹状体、海马、下丘脑、丘脑、中脑及脑干等脑区.这些脑组织被制成匀浆并用HPLC荧光检测法测量其组胺含量.结果显示暗时处死时,H1R基因敲除型小鼠海马、丘脑、中脑及脑干中的组胺含量明显低于野生型小鼠.明时处死时,野生型小鼠各脑区组胺含量均较暗时处死显著降低,但这一变化在H1R基因敲除型小鼠中并未观察到.这些表明作为组胺的功能靶,H1R不仅介导组胺的功能,而且调节大脑中组胺含量与释放的昼夜节律.     

Anti-nociceptive role of neuropeptide Y in the nucleus accumbens in rats with inflammation, an effect modulated by mu- and kappa-opioid receptors

Recent study in our laboratory showed that neuropeptide Y (NPY) plays an antinociceptive role in the nucleus accumbens (NAc) in intact rats. The present study was performed to further investigate the effect of NPY in nociceptive modulation in the NAc of rats with inflammation, and the possible interaction between NPY and the opioid systems. Experimental inflammation was induced by subcutaneous injection of carrageenan into the left hindpaw of rats. Intra-NAc administration of NPY induced a dose-dependent increase of hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in rats with inflammation. The anti-nociceptive effect of NPY was significantly blocked by subsequent intra-NAc injection of the Y1 receptor antagonist NPY28-36, suggesting an involvement of Y1 receptor in the NPY-induced anti-nociception. Furthermore, intra-NAc administration of the opioid antagonist naloxone significantly antagonized the increased HWLs induced by preceding intra-NAc injection of NPY, suggesting an involvement of the endogenous opioid system in the NPY-induced anti-nociception in the NAc during inflammation. Moreover, the NPY-induced anti-nociception was attenuated by following intra-NAc injection of the μ-opioid antagonist β-funaltrexamine (β-FNA), and κ-opioid antagonist nor-binaltorphimine (nor-BNI), but not by δ-opioid antagonist naltrindole, indicating that μ- and κ-opioid receptors, not δ-opioid receptor, are involved in the NPY-induced anti-nociception in the NAc in rats with inflammation.     

Calmodulin modulation of ion channels and receptors

Ion channels and receptors are the structural basis for neural signaling and transmission. Recently, the function of ion channels and receptors has been demonstrated to be modulated by many intracellular and extracellular chemicals and signaling molecules. Increasing evidence indicates that the complexity and plasticity of the function of central nervous system is determined by the modulation of ion channels and receptors. Among various mechanisms, Ca 2+ signaling pathways play important roles in neuronal activity and some pathological changes. Ca 2+ influx through ion channels and receptors can modulate its further influx in a feedback way or modulate other ion channels and receptors. The common feature of the modulation is that Ca 2+ /calmodulin (CaM) is the universal mediator. CaM maintains the coordination among ion channels/receptors and intracellular Ca 2+ homeostasis by feedback modulation of ion channels/receptors activity. This review focuses on the modulating processes of ion channels and receptors mediated by CaM, and further elucidates the mechanisms of Ca 2+ signaling.