AIM:To investigate the mechanism of gastric mucosal demage induced by water immersion restraint stress(WRS) and its prevention by growth hormone releasing peptide-6(GHRP-6).METHODS:Male Wistar rats were subjected to c...AIM:To investigate the mechanism of gastric mucosal demage induced by water immersion restraint stress(WRS) and its prevention by growth hormone releasing peptide-6(GHRP-6).METHODS:Male Wistar rats were subjected to conscious or unconscious(anesthetized) WRS,simple restraint(SR),free swimming(FS),non-water fluid immersion,immersion without water contact,or rats were placed in a cage surrounded by sand.To explore the sensitivity structures that influence the stress reaction besides skin stimuli,a group the rats had their eyes occluded.Cervical bilateral trunk vagotomy or atropine injection was performed in some rats to assess the parasympathetic role in mucosal damage.Gastric mucosal lesions,acid output and heart rate variability were measured.Plasma renin,endothelin-1 and thromboxane B2 and gastric heat shock protein 70 were also assayed.GHRP-6 was injected [intraperitoneal(IP) or intracerebroventricular(ICV)] 2 h before the onset of stress to observe its potential prevention of the mucosal lesion.RESULTS:WRS for 6 h induced serious gastric mucosal lesion [lesion area,WRS 81.8 ± 6.4 mm 2 vs normal control 0.0 ± 0.0 mm 2,P < 0.01],decreased the heart rate,and increased the heart rate variability and gastric acid secretion,suggesting an increase in vagal nervecarrying stimuli.The mucosal injury was inversely correlated with water temperature(lesion area,WRS at 35 ℃ 56.4 ± 5.2 mm 2 vs WRS at 23 ℃ 81.8 ± 6.4 mm 2,P < 0.01) and was consciousness-dependent.The injury could not be prevented by eye occlusion,but could be prevented by avoiding contact of the rat body with the water by dressing it in an impermeable plastic suit.When water was replaced by vegetable oil or liquid paraffin,there were gastric lesions in the same grade of water immersion.When rat were placed in a cage surrounded by sand,there were no gastric lesions.All these data point to a remarkable importance of cutenuous information transmitted to the high neural center that by vagal nerves reaching the gastric mucosa.FS alone also induced serious gastric injury,but SR could not induce gastric injury.Bilateral vagotomy or atropine prevented the WRS-induced mucosal lesion,indicating that increased outflow from the vagal center is a decisive factor in WRS-induced gastric injury.The mucosal lesions were prevented by prior injection of GHRP-6 via IP did,but not via ICV,suggesting that the protection is peripheral,although a sudden injection is not equivalent to a physiological release and uptake,which eventually may affect the vagal center.CONCLUSION:From the central nervous system,vagal nerves carry the cutaneous stimuli brought about by the immersion restraint,an experimental model for inducing acute gastric erosions.GHRP-6 prevents the occurrence of these lesions.展开更多
Poneratoxin （PoTX） is an insect neuropeptide isolated from ant venom. It was previously demonstrated that administration of synthetic PoTX into the lateral brain ventricle （icv） induced in rats significant antinoc...Poneratoxin （PoTX） is an insect neuropeptide isolated from ant venom. It was previously demonstrated that administration of synthetic PoTX into the lateral brain ventricle （icv） induced in rats significant antinociceptive effect. Moreover it was demonstrated that this effect was not mediated by opioid receptors. The aim of present study was to determine other probable mechanisms mediating antinociceptive effect of PoTX, above all： （1） to check if insect-derived pentapeptide Any-GS may influence on PoTX-induced analgesia in rats, and （2） to estimate the role of voltage-gated sodium channels in rat＇s brain in antinociceptive effect of PoTX. The study was performed on adult, female wistar rats, which a week before experiments were implanted with polyethylene cannulas into the lateral brain ventricle （icv）. Antinociceptive effect of PoTX applied directly icv was determined in rats by the test of the tail immersion. PoTX applied icv at the dose of 1 or 5 nmol induced significant antinociceptive effect in rats. Pretreatment rats with equimolar dose of 1 or 5 nmol of veratridine, an agent, which opens voltage-gated sodium channels in neurons of rat brain, did not modify effect of PoTX. On the other hand, prior icv administration of pentapeptide Any-GS significantly inhibited antinociceptive effect of both icv doses of 1 and 5 nmols of PoTX. The results of the present study demonstrated antagonistic effect Any-GS against PoTX-induced analgesia. Thus blocking effect Any-GS on PoTX-induced analgesia indicates that this insect peptide is a probable antagonist of PoTX.展开更多
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
基金Supported by National Natural Science Foundation of China, No.81071072,No.31171088(to Cao JM) and No.81000060(to Gao X)
文摘AIM:To investigate the mechanism of gastric mucosal demage induced by water immersion restraint stress(WRS) and its prevention by growth hormone releasing peptide-6(GHRP-6).METHODS:Male Wistar rats were subjected to conscious or unconscious(anesthetized) WRS,simple restraint(SR),free swimming(FS),non-water fluid immersion,immersion without water contact,or rats were placed in a cage surrounded by sand.To explore the sensitivity structures that influence the stress reaction besides skin stimuli,a group the rats had their eyes occluded.Cervical bilateral trunk vagotomy or atropine injection was performed in some rats to assess the parasympathetic role in mucosal damage.Gastric mucosal lesions,acid output and heart rate variability were measured.Plasma renin,endothelin-1 and thromboxane B2 and gastric heat shock protein 70 were also assayed.GHRP-6 was injected [intraperitoneal(IP) or intracerebroventricular(ICV)] 2 h before the onset of stress to observe its potential prevention of the mucosal lesion.RESULTS:WRS for 6 h induced serious gastric mucosal lesion [lesion area,WRS 81.8 ± 6.4 mm 2 vs normal control 0.0 ± 0.0 mm 2,P < 0.01],decreased the heart rate,and increased the heart rate variability and gastric acid secretion,suggesting an increase in vagal nervecarrying stimuli.The mucosal injury was inversely correlated with water temperature(lesion area,WRS at 35 ℃ 56.4 ± 5.2 mm 2 vs WRS at 23 ℃ 81.8 ± 6.4 mm 2,P < 0.01) and was consciousness-dependent.The injury could not be prevented by eye occlusion,but could be prevented by avoiding contact of the rat body with the water by dressing it in an impermeable plastic suit.When water was replaced by vegetable oil or liquid paraffin,there were gastric lesions in the same grade of water immersion.When rat were placed in a cage surrounded by sand,there were no gastric lesions.All these data point to a remarkable importance of cutenuous information transmitted to the high neural center that by vagal nerves reaching the gastric mucosa.FS alone also induced serious gastric injury,but SR could not induce gastric injury.Bilateral vagotomy or atropine prevented the WRS-induced mucosal lesion,indicating that increased outflow from the vagal center is a decisive factor in WRS-induced gastric injury.The mucosal lesions were prevented by prior injection of GHRP-6 via IP did,but not via ICV,suggesting that the protection is peripheral,although a sudden injection is not equivalent to a physiological release and uptake,which eventually may affect the vagal center.CONCLUSION:From the central nervous system,vagal nerves carry the cutaneous stimuli brought about by the immersion restraint,an experimental model for inducing acute gastric erosions.GHRP-6 prevents the occurrence of these lesions.
文摘Poneratoxin （PoTX） is an insect neuropeptide isolated from ant venom. It was previously demonstrated that administration of synthetic PoTX into the lateral brain ventricle （icv） induced in rats significant antinociceptive effect. Moreover it was demonstrated that this effect was not mediated by opioid receptors. The aim of present study was to determine other probable mechanisms mediating antinociceptive effect of PoTX, above all： （1） to check if insect-derived pentapeptide Any-GS may influence on PoTX-induced analgesia in rats, and （2） to estimate the role of voltage-gated sodium channels in rat＇s brain in antinociceptive effect of PoTX. The study was performed on adult, female wistar rats, which a week before experiments were implanted with polyethylene cannulas into the lateral brain ventricle （icv）. Antinociceptive effect of PoTX applied directly icv was determined in rats by the test of the tail immersion. PoTX applied icv at the dose of 1 or 5 nmol induced significant antinociceptive effect in rats. Pretreatment rats with equimolar dose of 1 or 5 nmol of veratridine, an agent, which opens voltage-gated sodium channels in neurons of rat brain, did not modify effect of PoTX. On the other hand, prior icv administration of pentapeptide Any-GS significantly inhibited antinociceptive effect of both icv doses of 1 and 5 nmols of PoTX. The results of the present study demonstrated antagonistic effect Any-GS against PoTX-induced analgesia. Thus blocking effect Any-GS on PoTX-induced analgesia indicates that this insect peptide is a probable antagonist of PoTX.
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.
