The study was undertaken in order to evaluate effect of synthetic insect neuropeptide leucopyrokinin analog, [D-Ala5]-[2-8]-LPK, on analgesia induced by selective agonists of/a-, 6- and l〈-opioid receptors. The study...The study was undertaken in order to evaluate effect of synthetic insect neuropeptide leucopyrokinin analog, [D-Ala5]-[2-8]-LPK, on analgesia induced by selective agonists of/a-, 6- and l〈-opioid receptors. The study was performed on male Wistar rats, which a week before the experiments were implanted with polyethylene cannulas into the lateral brain ventricle （icv）. Effect of prior administration of [D-Ala5]-[2-8]-LPK on analgesia induced in rats by next icv administration of equimolar dose of μ-, δ- and -opioid agonists： DAMGO, DPDPE and GR fumarate respectively, was evaluated. Antinociceptive effect was determined in rats by the test of the tail immersion. It was found that two doses of 5 and 10 nmols icv of [D-AlaS]-[2-8]-LPK inhibited analgesia in rats by equimolar doses of DAMGO. This analog also transiently （only in two time intervals） and in one dose of 10 nmols inhibited analgesia induced in rats by icv administration of equimolar DPDPE dose of 10 nmols icv. Obtained results indicate that [D-AlaS]-[2-8]-LPK inhibits antinociceptive effect of DAMGO and in part of DPDPE, i.e. mainly antagonized ~t-opioid receptors. These results correspond with results of our previous study that selective antagonists of μ- and δ-opioid receptors blocked antinociceptive effect of synthetic insect neuropeptide leucopyrokinin and of it active analog [2-8]-leucopyrokinin. We regard that [D-AIaS]-[2-8]-LPK, the first discovered antagonist of leucopyrokinin may be a useful as a probable tool substance in the study of biological effects of insect-derived peptides either in invertebrates or in mammals.展开更多
This study was aimed to investigate the role of the delta-opioid receptor （DOR）-β-arrestinl-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis （UC） and the intervention effects of oxymatr...This study was aimed to investigate the role of the delta-opioid receptor （DOR）-β-arrestinl-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis （UC） and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into nor- mal group, model group, oxymatrine-treated group and mesalazine-treated group （n=10 each） at ran- dom. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/（kg·day）] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/（kg·day）] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expres- sion levels of DOR, β-arrestinl and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction （RT-PCR）, respectively. It was found that the expression levels of DOR, [3-arrestinl and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups （P〈0.05）. They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group （P〈0.05）. No statistically significant difference was noted in these indices between mesalazine- and oxyma- trine-treated groups （P〉0.05）. This study indicated that the DOR-β-arrestinl-Bcl-2 signal transduc- tion pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the de- velopment of UC by regulating the DOR-β-arrestin 1-Bcl-2 signal transduction pathway.展开更多
文摘The study was undertaken in order to evaluate effect of synthetic insect neuropeptide leucopyrokinin analog, [D-Ala5]-[2-8]-LPK, on analgesia induced by selective agonists of/a-, 6- and l〈-opioid receptors. The study was performed on male Wistar rats, which a week before the experiments were implanted with polyethylene cannulas into the lateral brain ventricle （icv）. Effect of prior administration of [D-Ala5]-[2-8]-LPK on analgesia induced in rats by next icv administration of equimolar dose of μ-, δ- and -opioid agonists： DAMGO, DPDPE and GR fumarate respectively, was evaluated. Antinociceptive effect was determined in rats by the test of the tail immersion. It was found that two doses of 5 and 10 nmols icv of [D-AlaS]-[2-8]-LPK inhibited analgesia in rats by equimolar doses of DAMGO. This analog also transiently （only in two time intervals） and in one dose of 10 nmols inhibited analgesia induced in rats by icv administration of equimolar DPDPE dose of 10 nmols icv. Obtained results indicate that [D-AlaS]-[2-8]-LPK inhibits antinociceptive effect of DAMGO and in part of DPDPE, i.e. mainly antagonized ~t-opioid receptors. These results correspond with results of our previous study that selective antagonists of μ- and δ-opioid receptors blocked antinociceptive effect of synthetic insect neuropeptide leucopyrokinin and of it active analog [2-8]-leucopyrokinin. We regard that [D-AIaS]-[2-8]-LPK, the first discovered antagonist of leucopyrokinin may be a useful as a probable tool substance in the study of biological effects of insect-derived peptides either in invertebrates or in mammals.
基金supported by grants from the National Nature Science Foundation of China(No.81072944,and No.81273908)Nature Science Foundation of Hubei Province of China(No.2011CDB379)+1 种基金Postdoctoral Science Foundation of China(No.2012M510120)Doctor Fund Project of Higher Education of Ministry of Education of China(No.20110142120096)
文摘This study was aimed to investigate the role of the delta-opioid receptor （DOR）-β-arrestinl-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis （UC） and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into nor- mal group, model group, oxymatrine-treated group and mesalazine-treated group （n=10 each） at ran- dom. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/（kg·day）] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/（kg·day）] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expres- sion levels of DOR, β-arrestinl and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction （RT-PCR）, respectively. It was found that the expression levels of DOR, [3-arrestinl and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups （P〈0.05）. They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group （P〈0.05）. No statistically significant difference was noted in these indices between mesalazine- and oxyma- trine-treated groups （P〉0.05）. This study indicated that the DOR-β-arrestinl-Bcl-2 signal transduc- tion pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the de- velopment of UC by regulating the DOR-β-arrestin 1-Bcl-2 signal transduction pathway.
