Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of ...Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of thioperamide during brain edema in a rat model of neonatal hypoxic ischemic encephalopathy. Our results showed that thioperamide significantly decreased brain water content and malondialdehyde levels, while significantly increased histamine levels and superoxide dismutase activity in the hippocampus. This evidence demonstrates that thioperamide could pre vent oxidative damage and attenuate brain edema following neonatal hypoxicischemic encepha Iopathy. We further observed that changes in the above indexes occurred after combined treatment of thioperamide with the H1 receptor antagonist, pyrilamine, and the H2 receptor antagonist, ci metidine. Experimental findings indicated that pyrilamine reversed the effects of thioperamide; however, cimetidine had no significant influence on the effects of thioperamide. Our present findings suggest that thioperamide can increase brain histamine content and attenuate brain edema and oxidative damage by acting in combination with postsynaptic H1 receptors in a rat model of neo natal hypoxicischemic encephalopathy.展开更多
Chronic cough is a troublesome problem and it is frequently associated with diseases such as gastroesophageal reflux, asthma and upper airway diseases—so called diagnostic triade. The magnitude and severity of cough ...Chronic cough is a troublesome problem and it is frequently associated with diseases such as gastroesophageal reflux, asthma and upper airway diseases—so called diagnostic triade. The magnitude and severity of cough is strongly associated with the ongoing nasal inflammation in subjects with rhinosinusitis and treatment of nasal inflammation leads to the down regulation of pathologically up-regulated cough. Histamine plays a key role in the inflammation of the upper airways of different aetiologies;therefore histamine receptors seem to be promising targets. The aim of our study was to ascertain the effect of H<sub>3</sub>R agonist imetit and H<sub>3</sub>R antagonist thioperamide on cough and symptoms of allergic rhinitis (AR) in an animal model of upper airway cough syndrome in ovalbumin sensitized guinea pigs. OVA sensitized guinea pigs (n = 10) were repeatedly challenged with i.n. allergen-OVA to induce allergic rhinitis and to enhance cough reflex according to the validated model of experimental allergic rhinitis. Animals were pre-treated by i.p. administration of imetit (1 mg/kg and 2 mg/kg of body weight) and thioperamide 30 min. prior i.n. OVA administration. Rhinitis evaluation was based on the occurrence of typical symptoms. The effect on cough was assessed from the response to inhalation of citric acid (0.4 M, 10 min), final cough count and cough latency were analysed from the airflow traces, cough motor pattern and the cough sound. AR up-regulated the cough response from 9 ± 2 to 16 ± 1 cough per provocation, med ± IQR, p < 0.05 and shortened cough latency. Imetit (1 mg/kg) suppressed nasal symptoms and decreased number of cough from 16 ± 1 to 12 ± 1;however the data did not reach significance. Imetit (2 mg/kg) significantly suppressed the nasal symptoms, and number of coughs from 16 ± 1 to 6 ± 2, med ± IQR, p < 0.05. Thioperamide (5 mg/kg of body weight) did not have expected effects on tested parameters. H3R agonist imetit, unlike H3R antagonist thioperamide has antitussive potential and ability to suppress nasal symptoms in animal model of allergic rhinitis.展开更多
Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed...Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H3 receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole （PTZ）-kindling epilepsy in rats. Methods Chemical kindling was elicited by repeated intraperitoneal （ip） injections of a subconvulsant dose of PTZ （35 mg/kg） once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein （p-CREB） was tested by Western blotting in hippocampus. Results Intracerebroventricular （icv） injections with thioperamide （10 μg, 20 μg） 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide. Conclusions Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.展开更多
AIM:To test the hypothesis that histamine 3 receptor (H3R)activation during Helicobacter infection inhibits gastric acid secretion in vivo and in vitro.METHODS:Helicobacter felis(H.felis)infected and uninfected C57Bl/...AIM:To test the hypothesis that histamine 3 receptor (H3R)activation during Helicobacter infection inhibits gastric acid secretion in vivo and in vitro.METHODS:Helicobacter felis(H.felis)infected and uninfected C57Bl/6 mice were infused with either PBS or the H3 receptor antagonist thioperamide(THIO)for 12 wk.After treatment,mice were analyzed for morphological changes and gastric acid content.Total RNA was prepared from the stomachs of each group and analyzed for changes in somatostatin and gastrin mRNA abundance by real time-polymerase chain reaction(RTPCR).Location of H3 receptors in the stomach was analyzed by co-localization using antibodies specific for the H3 receptor and parietal cell marker H + ,K + -ATPase βsubunit. RESULTS:Inflammation and parietal cell atrophy was observed after 12 wk of H.felis infection.Interestingly, treatment with the H3R antagonist thioperamide(THIO) prior to and during infection prevented H.felis-induced inflammation and atrophy.Compared to the uninfected controls,infected mice also had significantly decreased gastric acid.After eradication of H.felis with THIO treatment,gastric acidity was restored.Compared to the control mice,somatostatin mRNA abundance was decreased while gastrin gene expression was elevated during infection.Despite elevated gastric acid levels, after eradication of H.felis with THIO,somatostatin mRNA was elevated whereas gastrin mRNA was suppressed.Immunofluorescence revealed the presence of H3 receptors on the parietal cells,somatostatin-secreting D-cells as well as the inflammatory cells. CONCLUSION:This study shows that during H.felis infection,gastric acidity is suppressed as a consequence of an inhibitory effect on the parietal cell by H3R activation.The stimulation of gastric mucosal H3Rs increases gastrin expression and release by inhibiting release of somatostatin.展开更多
基金supported by Jilin Provincial Science and Technology Department Foundation ofChina, No. 200905134
文摘Thioperamide, a selective histamine H3 receptor antagonist, can increase histamine content in the brain, improve brain edema, and exert a neuroprotective effect. This study aimed to examine the mechanism of action of thioperamide during brain edema in a rat model of neonatal hypoxic ischemic encephalopathy. Our results showed that thioperamide significantly decreased brain water content and malondialdehyde levels, while significantly increased histamine levels and superoxide dismutase activity in the hippocampus. This evidence demonstrates that thioperamide could pre vent oxidative damage and attenuate brain edema following neonatal hypoxicischemic encepha Iopathy. We further observed that changes in the above indexes occurred after combined treatment of thioperamide with the H1 receptor antagonist, pyrilamine, and the H2 receptor antagonist, ci metidine. Experimental findings indicated that pyrilamine reversed the effects of thioperamide; however, cimetidine had no significant influence on the effects of thioperamide. Our present findings suggest that thioperamide can increase brain histamine content and attenuate brain edema and oxidative damage by acting in combination with postsynaptic H1 receptors in a rat model of neo natal hypoxicischemic encephalopathy.
文摘Chronic cough is a troublesome problem and it is frequently associated with diseases such as gastroesophageal reflux, asthma and upper airway diseases—so called diagnostic triade. The magnitude and severity of cough is strongly associated with the ongoing nasal inflammation in subjects with rhinosinusitis and treatment of nasal inflammation leads to the down regulation of pathologically up-regulated cough. Histamine plays a key role in the inflammation of the upper airways of different aetiologies;therefore histamine receptors seem to be promising targets. The aim of our study was to ascertain the effect of H<sub>3</sub>R agonist imetit and H<sub>3</sub>R antagonist thioperamide on cough and symptoms of allergic rhinitis (AR) in an animal model of upper airway cough syndrome in ovalbumin sensitized guinea pigs. OVA sensitized guinea pigs (n = 10) were repeatedly challenged with i.n. allergen-OVA to induce allergic rhinitis and to enhance cough reflex according to the validated model of experimental allergic rhinitis. Animals were pre-treated by i.p. administration of imetit (1 mg/kg and 2 mg/kg of body weight) and thioperamide 30 min. prior i.n. OVA administration. Rhinitis evaluation was based on the occurrence of typical symptoms. The effect on cough was assessed from the response to inhalation of citric acid (0.4 M, 10 min), final cough count and cough latency were analysed from the airflow traces, cough motor pattern and the cough sound. AR up-regulated the cough response from 9 ± 2 to 16 ± 1 cough per provocation, med ± IQR, p < 0.05 and shortened cough latency. Imetit (1 mg/kg) suppressed nasal symptoms and decreased number of cough from 16 ± 1 to 12 ± 1;however the data did not reach significance. Imetit (2 mg/kg) significantly suppressed the nasal symptoms, and number of coughs from 16 ± 1 to 6 ± 2, med ± IQR, p < 0.05. Thioperamide (5 mg/kg of body weight) did not have expected effects on tested parameters. H3R agonist imetit, unlike H3R antagonist thioperamide has antitussive potential and ability to suppress nasal symptoms in animal model of allergic rhinitis.
基金This study was supported by grants from the Natural Science Foundation of Zhejiang Province （No. Y2090184） and the Project of Chinese Traditional Medicine of Zhejiang Province （No. 2006Y005）.
文摘Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H3 receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole （PTZ）-kindling epilepsy in rats. Methods Chemical kindling was elicited by repeated intraperitoneal （ip） injections of a subconvulsant dose of PTZ （35 mg/kg） once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein （p-CREB） was tested by Western blotting in hippocampus. Results Intracerebroventricular （icv） injections with thioperamide （10 μg, 20 μg） 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide. Conclusions Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.
基金Supported in part by Public Health Service Grants R37-DK45729(JLM)Michigan Gastrointestinal Peptide Research Center Pilot Feasibility Grant P30-DK34933(YZ)National Health and Medical Research Council of Australia Grant 350234(AS)
文摘AIM:To test the hypothesis that histamine 3 receptor (H3R)activation during Helicobacter infection inhibits gastric acid secretion in vivo and in vitro.METHODS:Helicobacter felis(H.felis)infected and uninfected C57Bl/6 mice were infused with either PBS or the H3 receptor antagonist thioperamide(THIO)for 12 wk.After treatment,mice were analyzed for morphological changes and gastric acid content.Total RNA was prepared from the stomachs of each group and analyzed for changes in somatostatin and gastrin mRNA abundance by real time-polymerase chain reaction(RTPCR).Location of H3 receptors in the stomach was analyzed by co-localization using antibodies specific for the H3 receptor and parietal cell marker H + ,K + -ATPase βsubunit. RESULTS:Inflammation and parietal cell atrophy was observed after 12 wk of H.felis infection.Interestingly, treatment with the H3R antagonist thioperamide(THIO) prior to and during infection prevented H.felis-induced inflammation and atrophy.Compared to the uninfected controls,infected mice also had significantly decreased gastric acid.After eradication of H.felis with THIO treatment,gastric acidity was restored.Compared to the control mice,somatostatin mRNA abundance was decreased while gastrin gene expression was elevated during infection.Despite elevated gastric acid levels, after eradication of H.felis with THIO,somatostatin mRNA was elevated whereas gastrin mRNA was suppressed.Immunofluorescence revealed the presence of H3 receptors on the parietal cells,somatostatin-secreting D-cells as well as the inflammatory cells. CONCLUSION:This study shows that during H.felis infection,gastric acidity is suppressed as a consequence of an inhibitory effect on the parietal cell by H3R activation.The stimulation of gastric mucosal H3Rs increases gastrin expression and release by inhibiting release of somatostatin.
