Key Laboratory for Gastrointestinal Diseases of Gansu Province

Lanzhou, China

Key Laboratory for Gastrointestinal Diseases of Gansu Province

Lanzhou, China
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He C.,Lanzhou University | Li H.,Lanzhou University | Zhang J.,Lanzhou University | Kang Y.,Lanzhou University | And 5 more authors.
Journal of Pharmacy and Pharmacology | Year: 2017

Objectives: Chimeric peptide MCRT, based on morphiceptin and PFRTic-NH2, was a bifunctional ligand of μ- and δ-opioid receptors (MOR-DOR) and produced potent analgesia in tail-withdrawal test. The study focused on the supraspinal effects of morphiceptin, PFRTic-NH2 and MCRT on gastrointestinal motility. Moreover, opioid receptor antagonists, naloxone (non-selective), cyprodime (MOR selective) and naltrindole (DOR selective) were utilized to explore the mechanisms. Methods: Intracerebroventricular administration was achieved via the implanted cannula. Gastric emptying and intestinal transit were measured to evaluate gastrointestinal motility. Key findings: (1) At supraspinal level, morphiceptin, PFRTic-NH2 and MCRT significantly decreased gastric emptying and intestinal transit; (2) MCRT at 1 nmol/mouse, far higher than its analgesic dose (ED50 = 29.8 pmol/mouse), failed to regulate the gastrointestinal motility; (3) MCRT-induced gastrointestinal dysfunction could be completely blocked by naloxone and naltrindole, but not affected by cyprodime. Conclusions: (1) Morphiceptin and PFRTic-NH2 played important roles in the regulation of gastrointestinal motility; (2) MCRT possessed higher bioactivity of pain relief than gastrointestinal regulation, suggesting its promising analgesic property; (3) MCRT-induced motility disorders were sensitive to DOR but not to MOR blockade, indicating the pain-relieving specificity of speculated MOR subtype or splice variant or MOR-DOR heterodimer. © 2017 Royal Pharmaceutical Society


Zhang J.,Institute of Biochemistry and Molecular Biology | He C.,Institute of Biochemistry and Molecular Biology | Pi X.,Institute of Biochemistry and Molecular Biology | Wang Y.,Institute of Biochemistry and Molecular Biology | And 4 more authors.
European Journal of Pharmacology | Year: 2016

The interactions of the chimeric peptide MCRT (YPFPFRTic-NH2), based on morphiceptin and neuropeptide FF derivative PFRTic-NH2, on the effects of endokinin A/B (EKA/B) on mean arterial blood pressure of the urethane-anaesthetized rat have been investigated in the absence and presence of tachykinin receptor antagonists, naloxone and NO synthase inhibitors. While MCRT produced dose dependent decreases in mean arterial pressure, in its presence only a small but statistically insignificant decreases in the magnitude and the time course of the depressor effect of EKA/B (10 nmol/kg) were observed. MCRT had little influence on the depressor effect of EKA/B (1 nmol/kg), but strongly potentiated that of EKA/B (100 nmol/kg). The tachykinin NK1receptor antagonist SR140333B (1 mg/kg) and the NK3antagonist SR142891 (2.79 mg/kg) both reduced the hypotensive effects of EKA/B and MCRT alone and blocked those of the two peptides in combination. The NK2antagonist GR159897 (4 mg/kg) partially blocked the depressor effects of EKA/B and MCRT alone. Naloxone (2 mg/kg) completely blocked the depressor effect of MCTR, but partially blocked that of EKA/B. The NO synthase inhibitor L-NAME (50 mg/kg) partially blocked the depressor effects of EKA/B, MCRT, and EKA/B + MCRT. These results could help to better understand the role of tachykinin receptors, opioid receptors and neuropeptide FF receptors in cardiovascular system. © 2016 Elsevier B.V.


He C.,Institute of Biochemistry and Molecular Biology | Gong J.,Institute of Biochemistry and Molecular Biology | Yang L.,Institute of Biochemistry and Molecular Biology | Zhang H.,Institute of Biochemistry and Molecular Biology | And 4 more authors.
Canadian Journal of Physiology and Pharmacology | Year: 2016

The present study focused on the interactive pain regulation of endokinin A/B (EKA/B, the common C-terminal decapeptide in EKA and EKB) or endokinin C/D (EKC/D, the common C-terminal duodecapeptide in EKC and EKD) on chimeric peptide MCRT (YPFPFRTic-NH2, based on YPFP-NH2 and PFRTic-NH2) at the supraspinal level in mice. Results demonstrated that the co-injection of nanomolar EKA/B and MCRT showed moderate regulation, whereas 30 pmol EKA/B had no effect on MCRT. The combination of EKC/D and MCRT produced enhanced antinociception, which was nearly equal to the sum of the mathematical values of single EKC/D and MCRT. Mechanism studies revealed that pre-injected naloxone attenuated the combination significantly compared with the equivalent analgesic effects of EKC/D alone, suggesting that EKC/D and MCRT might act on two totally independent pathways. Moreover, based on the above results and previous reports, we made two reasonable hypotheses to explain the cocktail-induced analgesia, which may potentially pave the way to explore the respective regulatory mechanisms of EKA/B, EKC/D, and MCRT and to better understand the complicated pain regulation of NK1 and µ opioid receptors, as follows: (1) MCRT and endomorphin-1 possibly activated different µ subtypes; and (2) picomolar EKA/B might motivate the endogenous NPFF system after NK1 activation. © 2016, Canadian Science Publishing. All rights reserved.


Zhou L.,Lanzhou University | Zhou L.,Key Laboratory for Gastrointestinal Diseases of Gansu Province | Yang Q.,Institute of Biochemistry and Molecular Biology | He C.,Institute of Biochemistry and Molecular Biology | And 4 more authors.
Neuropeptides | Year: 2015

The present study focused on the interactive effects of (Mpa6)-γ2-MSH-6-12 (Mpa, spinal level) and endokinin A/B (EKA/B, supraspinal level) on pain regulation in mice. EKA/B (30pmol) only weakened 100pmol Mpa-induced hyperalgesia at 5min, but could enhance it during 20-30min. However, EKA/B (100pmol) antagonized all dose levels of Mpa significantly at 5min and blocked them completely at 10min. EKA/B (3nmol) co-injected with Mpa presented marked analgesia at 5min and enduring hyperalgesia within 20-60min. To investigate the underlying mechanisms between Mpa and EKA/B, SR140333B and SR142801 (NK1 and NK3 receptor antagonists, respectively) were utilized. SR140333B had no influence on Mpa, while SR142801 potentiated it during 20-30min. Whereas, SR140333B and SR142801 could block the co-administration of Mpa and EKA/B (30pmol) separately at 5min and 30min. These phenomena might attribute to that these two antagonists promoted the antagonism of EKA/B (30pmol) at the early stage, while antagonized EKA/B preferentially in the latter period. SR140333B weakened the analgesia of EKA/B (3nmol), but produced no effect on Mpa. However, SR140333B failed to affect the co-injection of Mpa and EKA/B, which implied that EKA/B cooperated with Mpa prior to SR140333B. These results could potentially help to better understand the interaction of NK and MrgC receptors in pain regulation in mice. © 2015 Elsevier Ltd.


Chen Z.-F.,Lanzhou University | Chen Z.-F.,Key Laboratory for Gastrointestinal Diseases of Gansu Province | Huang S.-S.,Lanzhou University | Liu M.,Lanzhou University | And 13 more authors.
Journal of Practical Oncology | Year: 2014

Objective: To investigate the mechanisms related to the expression of E-cadherin regulated by COX-2 in human gastric cancer cells. Methods: Human gastric cancer SGC-7901 cells were treated with cyclooxygenase-2 (COX-2) inhibitor, celecoxib, at different concentrations for different durations. Western blot and real time quantitative RT-PCR were used to detect mRNA and protein expression of COX-2, NF-κB, Snail and E-cadherin. Results: The mRNA and protein expressions of COX-2, NF-κB and Snail in SGC-7901 cells declined and those of E-cadherin increased significantly after treated with celecoxib (P<0.05), in a dose- and time-dependent manner. The expression of COX-2 was positively correlated with NF-κB (r=0.881, P<0.01) and Snail (r=0.839, P<0.01) level, and was negatively correlated with E-cadherin level (r=-0.814, P<0.01). Conclusion: COX-2 may regulate the expression of E-cadherin through NF-κB and Snail signaling pathway during gastric cancer progression.

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