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
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
Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperre...Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure （MABP） in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats （250～300 g body weight, 2. 5～3 months old） were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ （0. 5 mg/kg） induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI（60 μg/kg）, 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.展开更多
The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and that is an endogenous ligant to a G protein-coupled receptor sequen...The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and that is an endogenous ligant to a G protein-coupled receptor sequentially related to the opioid receptors. OFQ was originally isolated from brain, but the presence of OFQ in peripheral tissues, especially in cardiovascular system, has not been clarified. The present study was designed to investigate the peripheral tissue distribution of OFQ precusor mRNA in stroke-prone spontaneously hypertensive rats (SHRSP) and compare the difference of OFQ precusor mRNA expression in aorta or cultured vascular smooth muscle cells (VSMCs) between SHRSP and wistar-Kyoto normotensive (WKY) rats. By using quantitative reverse transcription-polymerase chain reaction (RT-PCR), OFQ precusor mRNA was detected in aorta and ovary at high levels comparable with the amounts found in brain. Moderate expression was found in testis, while a little OFQ precusor mRNA could be detected in atrium. All other peripheral tissues examined from SHRSP, including ventricle, liver, lung and kidney, showed no expression of OFQ precusor mRNA. In the vascular system, OFQ precusor mRNA was expressed in aorta, pulmonary artery, renal artery and vein at high levels comparable with the amounts found in brain. We also found that OFQ precusor mRNA levels were much higher in aorta or cultured VSMCs from SHRSP than those from WKY rats. In conclusion, the present study has shown that OFQ precusor mRNA is present in some peripheral tissues, especially in cardiovascular and reproductive system, suggesting that OFQ possibly involves in the regulation of cardiovascular and reproductive functions.展开更多
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.
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Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure （MABP） in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats （250～300 g body weight, 2. 5～3 months old） were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ （0. 5 mg/kg） induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI（60 μg/kg）, 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.
文摘The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and that is an endogenous ligant to a G protein-coupled receptor sequentially related to the opioid receptors. OFQ was originally isolated from brain, but the presence of OFQ in peripheral tissues, especially in cardiovascular system, has not been clarified. The present study was designed to investigate the peripheral tissue distribution of OFQ precusor mRNA in stroke-prone spontaneously hypertensive rats (SHRSP) and compare the difference of OFQ precusor mRNA expression in aorta or cultured vascular smooth muscle cells (VSMCs) between SHRSP and wistar-Kyoto normotensive (WKY) rats. By using quantitative reverse transcription-polymerase chain reaction (RT-PCR), OFQ precusor mRNA was detected in aorta and ovary at high levels comparable with the amounts found in brain. Moderate expression was found in testis, while a little OFQ precusor mRNA could be detected in atrium. All other peripheral tissues examined from SHRSP, including ventricle, liver, lung and kidney, showed no expression of OFQ precusor mRNA. In the vascular system, OFQ precusor mRNA was expressed in aorta, pulmonary artery, renal artery and vein at high levels comparable with the amounts found in brain. We also found that OFQ precusor mRNA levels were much higher in aorta or cultured VSMCs from SHRSP than those from WKY rats. In conclusion, the present study has shown that OFQ precusor mRNA is present in some peripheral tissues, especially in cardiovascular and reproductive system, suggesting that OFQ possibly involves in the regulation of cardiovascular and reproductive functions.
