AIM: To study the effect of the opioid-receptor like-1(ORL1) agonist nociceptin on gastrointestinal(GI)myenteric neurotransmission and motility. METHODS: Reverse transcriptase- polymerase chain reaction and immunohist...AIM: To study the effect of the opioid-receptor like-1(ORL1) agonist nociceptin on gastrointestinal(GI)myenteric neurotransmission and motility. METHODS: Reverse transcriptase- polymerase chain reaction and immunohistochemistry were used to localize nociceptin and ORL1 in mouse tissues. Intracellular electrophysiological recordings of excitatory and inhibitory junction potentials(EJP, IJP) were made in a chambered organ bath. Intestinal motility was measured in vivo. RESULTS: Nociceptin accelerated whole and upper GI transit, but slowed colonic expulsion in vivo in an ORL1-dependent manner, as shown using [Nphe1]NOC and AS ODN pretreatment. ORL1 and nociceptin immunoreactivity were found on enteric neurons. Nociceptin reduced the EJP and the nitric oxide-sensitive slow IJP in an ORL1-dependent manner, whereas the fast IJP was unchanged. Nociceptin further reduced the spatial spreading of the EJP up to 2 cm. CONCLUSION: Compounds acting at ORL1 are good candidates for the future treatment of disorders associated with increased colonic transit, such as diarrhea or diarrhea-predominant irritable bowel syndrome.展开更多
AIM： The utility of serum alpha-fetoprotein （α-FP） in the detection of hepatocellular carcinoma （HCC） is questionable. Very high circulating levels of nociceptin/ orphanin FQ （N/OFQ）, a ligand for a novel opio...AIM： The utility of serum alpha-fetoprotein （α-FP） in the detection of hepatocellular carcinoma （HCC） is questionable. Very high circulating levels of nociceptin/ orphanin FQ （N/OFQ）, a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis. METHODS： Plasma N/OFQ levels were measured by ELISA in 58 patients （28 HCC and 30 liver cirrhosis） and in 25 healthy controls. The values were correlated with clinical and laboratory features including α-FP. Spearman index, biserial correlation coefficient, non parametric combination （NPC） test and discriminant stepwise analysis were used for statistical evaluation of data.RESULTS： The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. α-FP serum levels〉200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including α-FP. By NPC test, HCC and cirrhotic patients were different with regard to α-FP （P = 0.000） but not in terms of nociceptin （P = 0.595）. By point biserial correlation, HCC presence was positively correlated with α-FP （rpb = 0.52, P = 0.000） but not with N/OFQ （rpb = 0.16, P = 0.157）. In a discriminant analysis, α-FP was significant in the Wilks test （Y = -0.709 ＋ 0.03 α-FP） and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than α-FP. CONCLUSION： Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.展开更多
Expression of opioid receptor-like receptor (ORL1)and its endogenous peptide agonist nociceptin/orphaninFo (N/OFQ) during mouse embryogenesis have been investigated. Transcripts of ORL1 and N/OFQ were detected by RT-P...Expression of opioid receptor-like receptor (ORL1)and its endogenous peptide agonist nociceptin/orphaninFo (N/OFQ) during mouse embryogenesis have been investigated. Transcripts of ORL1 and N/OFQ were detected by RT-PCR in mouse brain of day 8 embryo (E8)and the expression continued afterwards. Northern blotanalysis revealed abundant expression of ORL1 at postnatal day 1 (P1) and N/OFQ at E17 and P1 in the brain butnone was detected in other embryonic tissues. The presence of functional ORL1 in mouse embryonic brain wasalso confirmed by specific binding of [3H] N/OFQ (kd=1.3±0.5 nM and Bmax = 72±9 fmol/mg protein) as wellas by N/OFQ-stimulated G protein activation.展开更多
Nociceptin (NC) and its 4 fragments have been synthesized by solid phase peptide synthesis. Their hypotensive activity and mechanism, MVD assay and structure-activity relationship have been investigated. Results show ...Nociceptin (NC) and its 4 fragments have been synthesized by solid phase peptide synthesis. Their hypotensive activity and mechanism, MVD assay and structure-activity relationship have been investigated. Results show that NC(1-13)NH2 is the smallest fragment that shares the same activity with NC. The truncation of C-terminal not only leads the decrease展开更多
为进一步了解孤啡肽在脊髓水平是否具有抗伤害及抗炎作用,本实验在具有多种痛行为表现的蜜蜂毒模型上观察了鞘内注射孤啡肽对大鼠一侧后足底注入蜜蜂毒所诱致的同侧自发缩足反射、原发热和机械性痛敏以及注射部位炎症反应的影响,同时观...为进一步了解孤啡肽在脊髓水平是否具有抗伤害及抗炎作用,本实验在具有多种痛行为表现的蜜蜂毒模型上观察了鞘内注射孤啡肽对大鼠一侧后足底注入蜜蜂毒所诱致的同侧自发缩足反射、原发热和机械性痛敏以及注射部位炎症反应的影响,同时观察了新的高选择性孤啡肽受体拮抗剂CompB的作用。结果表明:与生理盐水对照组比较,鞘内注射孤啡肽(3、10、30nmol/10μl)对蜜蜂毒诱发的自发缩足反射次数的抑制作用随剂量提高而增大,抑制率分别为37±7,43±6 and 57±11%(三个剂量vs对照,P<0.05);而对蜜蜂毒诱发的注射部位炎症反应(爪体积、爪背腹厚度和蛋白渗出的增加)无显著影响。CompB(30nmol)可完全翻转10nmol孤啡肽对自发缩足反射的抑制作用。鞘内单次或重复注射孤啡肽(10nmol/10μl)对蜜蜂毒诱致的原发性热和机械性痛敏的发生和维持均无作用。本实验结果提示,外源性孤啡肽在脊髓通过孤啡肽受体的介导产生一定的镇痛作用,但是它可能仅对持续性自发痛有抑制作用,而对热和机械性痛敏及炎症反应均无影响。展开更多
基金Supported by The Deutsche Forschungsgemeinschaft(STO 645/2-1 to Storr M and YU132/2-1 to Yuece B)the Society of Gastroenterology in Bavaria(to Storr M)+4 种基金the Frderprogramm für Forschung und Lehre of the Ludwig Maximilians University Munich to Yuece Bthe University of Calgary Research Grant Committee(to Storr M)the Iuventus Plus program of the Polish Ministry of Science and Higher Education(#0107/IP1/2013/72 to Fichna J)the grants from the Medical University of Lodz(#503/1-156-04/503-01 to Fichna J)National Science Centre(#UMO-2013/11/B/NZ7/01301 to Fichna J)
文摘AIM: To study the effect of the opioid-receptor like-1(ORL1) agonist nociceptin on gastrointestinal(GI)myenteric neurotransmission and motility. METHODS: Reverse transcriptase- polymerase chain reaction and immunohistochemistry were used to localize nociceptin and ORL1 in mouse tissues. Intracellular electrophysiological recordings of excitatory and inhibitory junction potentials(EJP, IJP) were made in a chambered organ bath. Intestinal motility was measured in vivo. RESULTS: Nociceptin accelerated whole and upper GI transit, but slowed colonic expulsion in vivo in an ORL1-dependent manner, as shown using [Nphe1]NOC and AS ODN pretreatment. ORL1 and nociceptin immunoreactivity were found on enteric neurons. Nociceptin reduced the EJP and the nitric oxide-sensitive slow IJP in an ORL1-dependent manner, whereas the fast IJP was unchanged. Nociceptin further reduced the spatial spreading of the EJP up to 2 cm. CONCLUSION: Compounds acting at ORL1 are good candidates for the future treatment of disorders associated with increased colonic transit, such as diarrhea or diarrhea-predominant irritable bowel syndrome.
文摘AIM： The utility of serum alpha-fetoprotein （α-FP） in the detection of hepatocellular carcinoma （HCC） is questionable. Very high circulating levels of nociceptin/ orphanin FQ （N/OFQ）, a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis. METHODS： Plasma N/OFQ levels were measured by ELISA in 58 patients （28 HCC and 30 liver cirrhosis） and in 25 healthy controls. The values were correlated with clinical and laboratory features including α-FP. Spearman index, biserial correlation coefficient, non parametric combination （NPC） test and discriminant stepwise analysis were used for statistical evaluation of data.RESULTS： The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. α-FP serum levels〉200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including α-FP. By NPC test, HCC and cirrhotic patients were different with regard to α-FP （P = 0.000） but not in terms of nociceptin （P = 0.595）. By point biserial correlation, HCC presence was positively correlated with α-FP （rpb = 0.52, P = 0.000） but not with N/OFQ （rpb = 0.16, P = 0.157）. In a discriminant analysis, α-FP was significant in the Wilks test （Y = -0.709 ＋ 0.03 α-FP） and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than α-FP. CONCLUSION： Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.
文摘Expression of opioid receptor-like receptor (ORL1)and its endogenous peptide agonist nociceptin/orphaninFo (N/OFQ) during mouse embryogenesis have been investigated. Transcripts of ORL1 and N/OFQ were detected by RT-PCR in mouse brain of day 8 embryo (E8)and the expression continued afterwards. Northern blotanalysis revealed abundant expression of ORL1 at postnatal day 1 (P1) and N/OFQ at E17 and P1 in the brain butnone was detected in other embryonic tissues. The presence of functional ORL1 in mouse embryonic brain wasalso confirmed by specific binding of [3H] N/OFQ (kd=1.3±0.5 nM and Bmax = 72±9 fmol/mg protein) as wellas by N/OFQ-stimulated G protein activation.
文摘Nociceptin (NC) and its 4 fragments have been synthesized by solid phase peptide synthesis. Their hypotensive activity and mechanism, MVD assay and structure-activity relationship have been investigated. Results show that NC(1-13)NH2 is the smallest fragment that shares the same activity with NC. The truncation of C-terminal not only leads the decrease
基金The work was supported by National Brain Science Basic Research Programme (No. G1999054004) and National Nature Science Foundation of China (No. 30000051, 30100052 and 30200077)
文摘为进一步了解孤啡肽在脊髓水平是否具有抗伤害及抗炎作用,本实验在具有多种痛行为表现的蜜蜂毒模型上观察了鞘内注射孤啡肽对大鼠一侧后足底注入蜜蜂毒所诱致的同侧自发缩足反射、原发热和机械性痛敏以及注射部位炎症反应的影响,同时观察了新的高选择性孤啡肽受体拮抗剂CompB的作用。结果表明:与生理盐水对照组比较,鞘内注射孤啡肽(3、10、30nmol/10μl)对蜜蜂毒诱发的自发缩足反射次数的抑制作用随剂量提高而增大,抑制率分别为37±7,43±6 and 57±11%(三个剂量vs对照,P<0.05);而对蜜蜂毒诱发的注射部位炎症反应(爪体积、爪背腹厚度和蛋白渗出的增加)无显著影响。CompB(30nmol)可完全翻转10nmol孤啡肽对自发缩足反射的抑制作用。鞘内单次或重复注射孤啡肽(10nmol/10μl)对蜜蜂毒诱致的原发性热和机械性痛敏的发生和维持均无作用。本实验结果提示,外源性孤啡肽在脊髓通过孤啡肽受体的介导产生一定的镇痛作用,但是它可能仅对持续性自发痛有抑制作用,而对热和机械性痛敏及炎症反应均无影响。
