The effects of centrally injected nitric oxide (NO) donors on gastric acid secretion were investigated in continuously perfused stomach of anesthetized rats. The lateral cerebroventricular (LV) injection of NOC5 (30 - 100 microg) and NOC12 (10 - 100 microg) dose-dependently stimulated gastric acid secretion. The LV injection of NOC18 (30 microg) also stimulated gastric acid secretion. The other type of NO donor, sodium nitroprusside (3 - 30 microg, LV), also dose-dependently stimulated gastric acid secretion. The effect of NOC5 at 100 microg was blocked by carboxy-PTIO, an NO scavenger, and by cervical vagotomy. Furthermore, NOC12 (30, 100 microg) dose-dependently stimulated gastric acid secretion in pylorus-ligated conscious rats. These results suggest that centrally injected NO donors stimulate gastric acid secretion in both conscious and anesthetized rats through vagus activation.
{"title":"Stimulatory effects of centrally injected nitric oxide donors on gastric acid secretion in anesthetized rats.","authors":"S. Tsuchiya, S. Horie, Kazuo Watanabe","doi":"10.1254/JJP.89.126","DOIUrl":"https://doi.org/10.1254/JJP.89.126","url":null,"abstract":"The effects of centrally injected nitric oxide (NO) donors on gastric acid secretion were investigated in continuously perfused stomach of anesthetized rats. The lateral cerebroventricular (LV) injection of NOC5 (30 - 100 microg) and NOC12 (10 - 100 microg) dose-dependently stimulated gastric acid secretion. The LV injection of NOC18 (30 microg) also stimulated gastric acid secretion. The other type of NO donor, sodium nitroprusside (3 - 30 microg, LV), also dose-dependently stimulated gastric acid secretion. The effect of NOC5 at 100 microg was blocked by carboxy-PTIO, an NO scavenger, and by cervical vagotomy. Furthermore, NOC12 (30, 100 microg) dose-dependently stimulated gastric acid secretion in pylorus-ligated conscious rats. These results suggest that centrally injected NO donors stimulate gastric acid secretion in both conscious and anesthetized rats through vagus activation.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"21 1","pages":"126-32"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81716732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pao‐Li Wang, M. Oido-Mori, T. Fujii, Y. Kowashi, M. Kikuchi, Y. Suetsugu, J. Tanaka, Y. Azuma, M. Shinohara, K. Ohura
The lipopolysaccharide (LPS) released by Porphyromonas gingivalis, a Gram-negative bacterium found in the periodontal pockets of patients with periodontitis, induces bone resorbing activity in vivo. We previously showed that a receptor for LPS on human gingival fibroblasts and gingival epithelial cells is CD14. In this study, we established a mouse model of experimental periodontitis by applying a P. gingivalis LPS solution to the buccal region of mice. P. gingivalis LPS-induced bone resorption and interleukin-6 production in the gingival tissues were significantly inhibited by pretreatment with anti-CD14 antibody for 5 weeks prior to LPS treatment. This result suggests that anti-CD14 antibody may be usable as a prototype for the development of drugs for the treatment of periodontal disease.
{"title":"Effect of anti-CD14 antibody on experimental periodontitis induced by Porphyromonas gingivalis lipopolysaccharide.","authors":"Pao‐Li Wang, M. Oido-Mori, T. Fujii, Y. Kowashi, M. Kikuchi, Y. Suetsugu, J. Tanaka, Y. Azuma, M. Shinohara, K. Ohura","doi":"10.1254/JJP.89.176","DOIUrl":"https://doi.org/10.1254/JJP.89.176","url":null,"abstract":"The lipopolysaccharide (LPS) released by Porphyromonas gingivalis, a Gram-negative bacterium found in the periodontal pockets of patients with periodontitis, induces bone resorbing activity in vivo. We previously showed that a receptor for LPS on human gingival fibroblasts and gingival epithelial cells is CD14. In this study, we established a mouse model of experimental periodontitis by applying a P. gingivalis LPS solution to the buccal region of mice. P. gingivalis LPS-induced bone resorption and interleukin-6 production in the gingival tissues were significantly inhibited by pretreatment with anti-CD14 antibody for 5 weeks prior to LPS treatment. This result suggests that anti-CD14 antibody may be usable as a prototype for the development of drugs for the treatment of periodontal disease.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"12 1","pages":"176-83"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76681948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Hasegawa, Toshinobu Sasaki, K. Sadakane, M. Tabuchi, Y. Takeda, M. Kimura, Y. Fujii
Ipecac syrup, prepared from a galentical ipecac, contains the nauseant alkaloids cephaeline and emetine. The involvement of receptors and serotonin- and dopamine-metabolizing enzymes in the emesis induced by ipecac syrup and these components was investigated. 1) In ferrets, the selective 5-HT3-receptor antagonist ondansetron (0.5 mg/kg, p.o.) prevented each emesis induced by TJN-119 (0.5 mL/kg, p.o.), cephaeline (0.5 mg/kg, p.o.) and emetine (5.0 mg/kg, p.o.), but the intraperitoneal administration of the selective dopamine D2-receptor antagonist sulpiride failed to significantly suppress the TJN-119, cephaeline and emetine-induced emesis at a dose of 0.1 mg/kg that blocked apomorphine-induced emesis. 2) In the receptor binding assays, cephaeline and emetine had a distinct affinity to 5-HT4 receptor, but no or weak affinity to 5-HT1A, 5-HT3, nicotine, M3, beta1, NK1, and D2 receptors. 3) Cephaeline and emetine did not affect activities of metabolic enzymes of 5-HT and dopamine (MAO-A, MAO-B, tryptophan 5-hydroxylase and tyrosine hydroxylase) in vitro. These results suggest that 5-HT3 receptor plays an important role in the emetic action of TJN-119, cephaeline and emetine, and the 5-HT4 receptor may be involved in their mechanisms.
{"title":"Studies for the emetic mechanisms of ipecac syrup (TJN-119) and its active components in ferrets: involvement of 5-hydroxytryptamine receptors.","authors":"M. Hasegawa, Toshinobu Sasaki, K. Sadakane, M. Tabuchi, Y. Takeda, M. Kimura, Y. Fujii","doi":"10.1254/JJP.89.113","DOIUrl":"https://doi.org/10.1254/JJP.89.113","url":null,"abstract":"Ipecac syrup, prepared from a galentical ipecac, contains the nauseant alkaloids cephaeline and emetine. The involvement of receptors and serotonin- and dopamine-metabolizing enzymes in the emesis induced by ipecac syrup and these components was investigated. 1) In ferrets, the selective 5-HT3-receptor antagonist ondansetron (0.5 mg/kg, p.o.) prevented each emesis induced by TJN-119 (0.5 mL/kg, p.o.), cephaeline (0.5 mg/kg, p.o.) and emetine (5.0 mg/kg, p.o.), but the intraperitoneal administration of the selective dopamine D2-receptor antagonist sulpiride failed to significantly suppress the TJN-119, cephaeline and emetine-induced emesis at a dose of 0.1 mg/kg that blocked apomorphine-induced emesis. 2) In the receptor binding assays, cephaeline and emetine had a distinct affinity to 5-HT4 receptor, but no or weak affinity to 5-HT1A, 5-HT3, nicotine, M3, beta1, NK1, and D2 receptors. 3) Cephaeline and emetine did not affect activities of metabolic enzymes of 5-HT and dopamine (MAO-A, MAO-B, tryptophan 5-hydroxylase and tyrosine hydroxylase) in vitro. These results suggest that 5-HT3 receptor plays an important role in the emetic action of TJN-119, cephaeline and emetine, and the 5-HT4 receptor may be involved in their mechanisms.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"81 1","pages":"113-9"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80089527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Overproduction of nitric oxide (NO) from inducible nitric oxide synthase (iNOS) is importantly involved in the pathogenesis of endotoxemia and atherosclerosis. Calcium antagonists are commonly used as cardiovascular drugs and have a beneficial effect on prolonging survival in various models of endotoxin shock. The present study was to investigate the effect of a calcium antagonist amlodipine on nitrite, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) formation and iNOS induction both in lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-treated rat aortic smooth muscle cells (RASMC) and in a rat model of endotoxemia. Incubation with amlodipine (0.1 - 10 microM) for 24 h resulted in a significant and dose-dependent attenuation in medium nitrite, TNF-alpha and IL-1beta formation as well as iNOS protein expression in LPS/IFN-gamma-treated RASMC. In addition, amlodipine inhibited leucigenin-induced superoxide formation in RASMC. In the rat endotoxic model, the serum nitrite/nitrate, TNF-alpha and IL-1beta levels as well as iNOS protein expression of lungs were also suppressed by administration of amlodipine (50 microg/kg, i.v.). These results suggest that amlodipine may exert vascular beneficial effects by suppressing pro-inflammatory cytokines and free radical generation as well as iNOS induction in smooth muscle cells during activation of inflammatory mechanism.
{"title":"Amlodipine inhibits pro-inflammatory cytokines and free radical production and inducible nitric oxide synthase expression in lipopolysaccharide/interferon-gamma-stimulated cultured vascular smooth muscle cells.","authors":"T. Chou, S. Yang, D. Pei","doi":"10.1254/JJP.89.157","DOIUrl":"https://doi.org/10.1254/JJP.89.157","url":null,"abstract":"Overproduction of nitric oxide (NO) from inducible nitric oxide synthase (iNOS) is importantly involved in the pathogenesis of endotoxemia and atherosclerosis. Calcium antagonists are commonly used as cardiovascular drugs and have a beneficial effect on prolonging survival in various models of endotoxin shock. The present study was to investigate the effect of a calcium antagonist amlodipine on nitrite, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) formation and iNOS induction both in lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-treated rat aortic smooth muscle cells (RASMC) and in a rat model of endotoxemia. Incubation with amlodipine (0.1 - 10 microM) for 24 h resulted in a significant and dose-dependent attenuation in medium nitrite, TNF-alpha and IL-1beta formation as well as iNOS protein expression in LPS/IFN-gamma-treated RASMC. In addition, amlodipine inhibited leucigenin-induced superoxide formation in RASMC. In the rat endotoxic model, the serum nitrite/nitrate, TNF-alpha and IL-1beta levels as well as iNOS protein expression of lungs were also suppressed by administration of amlodipine (50 microg/kg, i.v.). These results suggest that amlodipine may exert vascular beneficial effects by suppressing pro-inflammatory cytokines and free radical generation as well as iNOS induction in smooth muscle cells during activation of inflammatory mechanism.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"24 1","pages":"157-63"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80870738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Suzuki, Mayumi Suzuki, Yukika Kitamura, Saori Mori, Kazunori Sato, S. Dohi, Takashi Sato, A. Matsuura, A. Hiraide
In our previous study, beta-hydroxybutyrate (BHB) was found to prolong survival time and to inhibit cerebral edema by improving energy metabolism in the hypoxia, anoxia and global cerebral ischemia models. In this study, the cerebroprotective effect of BHB was examined in rats with permanent (p)-occlusion and transient (t)-occlusion of middle cerebral artery (MCA). BHB (30 mg x kg(-1) x h(-1) was continuously administered through the femoral vein. In rats with p-MCA occlusion, BHB significantly reduced infarct area at 24 h after the occlusion, but not at 72 h after the occlusion. In rats with 2-h t-MCA occlusion followed by 22-h reperfusion, BHB significantly reduced cerebral infarct area, edema formation, lipid peroxidation and neurological deficits. Moreover, in the t-MCA occlusion model, delayed administration of BHB started at 1 h after the initiation of the MCA occlusion also significantly reduced cerebral infarct area. Taking together the results obtained in our previous study into account, these results indicate that BHB decreased cerebral edema formation and infarct area by improving of the cerebral energy metabolism during ischemia and by inhibition of lipid peroxidation after reperfusion.
在我们前期的研究中发现，在缺氧、缺氧和全脑缺血模型中，β -羟基丁酸(BHB)通过改善能量代谢来延长存活时间和抑制脑水肿。本研究对大脑中动脉(MCA)永久性(p)闭塞和暂时性(t)闭塞大鼠进行脑保护作用的研究。经股静脉连续给予BHB (30mg x kg(-1) x h(-1))。在p-MCA闭塞的大鼠中，BHB在闭塞后24小时显著减少梗死面积，但在闭塞后72小时没有明显减少。在t-MCA闭塞2小时后再灌注22小时的大鼠中，BHB显著减少脑梗死面积、水肿形成、脂质过氧化和神经功能缺损。此外，在t-MCA闭塞模型中，在MCA闭塞开始后1小时延迟给药BHB也显著减少了脑梗死面积。综合我们之前的研究结果，这些结果表明，BHB通过改善缺血时的脑能量代谢和抑制再灌注后的脂质过氧化来减少脑水肿的形成和梗死面积。
{"title":"β-hydroxybutyrate, a cerebral function improving agent, protects rat brain against ischemic damage caused by permanent and transient focal cerebral ischemia","authors":"M. Suzuki, Mayumi Suzuki, Yukika Kitamura, Saori Mori, Kazunori Sato, S. Dohi, Takashi Sato, A. Matsuura, A. Hiraide","doi":"10.1254/JJP.89.36","DOIUrl":"https://doi.org/10.1254/JJP.89.36","url":null,"abstract":"In our previous study, beta-hydroxybutyrate (BHB) was found to prolong survival time and to inhibit cerebral edema by improving energy metabolism in the hypoxia, anoxia and global cerebral ischemia models. In this study, the cerebroprotective effect of BHB was examined in rats with permanent (p)-occlusion and transient (t)-occlusion of middle cerebral artery (MCA). BHB (30 mg x kg(-1) x h(-1) was continuously administered through the femoral vein. In rats with p-MCA occlusion, BHB significantly reduced infarct area at 24 h after the occlusion, but not at 72 h after the occlusion. In rats with 2-h t-MCA occlusion followed by 22-h reperfusion, BHB significantly reduced cerebral infarct area, edema formation, lipid peroxidation and neurological deficits. Moreover, in the t-MCA occlusion model, delayed administration of BHB started at 1 h after the initiation of the MCA occlusion also significantly reduced cerebral infarct area. Taking together the results obtained in our previous study into account, these results indicate that BHB decreased cerebral edema formation and infarct area by improving of the cerebral energy metabolism during ischemia and by inhibition of lipid peroxidation after reperfusion.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"17 1","pages":"36-43"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75602632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Yamamura, Kazuho Sakamoto, S. Ohya, K. Muraki, Y. Imaizumi
The mechanisms underlying the activation of large conductance Ca2+-activated K+ (BK) channel by nordihydroguaiaretic acid (NDGA) were examined in human embryonic kidney (HEK293) cells, where BK channel alpha (BKalpha) or a plus beta1 subunit (BKalphabeta1) was heterologously expressed, and also in freshly isolated porcine coronary arterial smooth muscle cells (PCASMCs). The activity of both BKalpha and BKalphabeta1 channels was increased by 10 microM NDGA in similar manners, indicating the selective action on the a subunit to increase Ca2+ sensitivity. The application of NDGA to PCASMCs induced outward current and hyperpolarization under voltage and current clamp, respectively, in a concentration-dependent manner (> or = 3 microM). These effects were blocked by 100 nM iberiotoxin. Electrical events induced by NDGA (> or = 10 microM) were, unexpectedly, associated with the increase in [Ca2+]i. After the treatment with caffeine and ryanodine, the [Ca2+]i increase by NDGA was markedly reduced and the hyperpolarization by NDGA was attenuated. The Ca2+ release by 10 microM NDGA was preceded by membrane depolarization of mitochondria. These results indicate that BK channel opening by NDGA in PCASMCs is due to the direct action on a subunit and also to Ca2+ release from sarcoplasmic reticulum, presumably via, at least in part, the inhibition of mitochondria respiration.
{"title":"Mechanisms underlying the activation of large conductance Ca2+-activated K+ channels by nordihydroguaiaretic acid.","authors":"H. Yamamura, Kazuho Sakamoto, S. Ohya, K. Muraki, Y. Imaizumi","doi":"10.1254/JJP.89.53","DOIUrl":"https://doi.org/10.1254/JJP.89.53","url":null,"abstract":"The mechanisms underlying the activation of large conductance Ca2+-activated K+ (BK) channel by nordihydroguaiaretic acid (NDGA) were examined in human embryonic kidney (HEK293) cells, where BK channel alpha (BKalpha) or a plus beta1 subunit (BKalphabeta1) was heterologously expressed, and also in freshly isolated porcine coronary arterial smooth muscle cells (PCASMCs). The activity of both BKalpha and BKalphabeta1 channels was increased by 10 microM NDGA in similar manners, indicating the selective action on the a subunit to increase Ca2+ sensitivity. The application of NDGA to PCASMCs induced outward current and hyperpolarization under voltage and current clamp, respectively, in a concentration-dependent manner (> or = 3 microM). These effects were blocked by 100 nM iberiotoxin. Electrical events induced by NDGA (> or = 10 microM) were, unexpectedly, associated with the increase in [Ca2+]i. After the treatment with caffeine and ryanodine, the [Ca2+]i increase by NDGA was markedly reduced and the hyperpolarization by NDGA was attenuated. The Ca2+ release by 10 microM NDGA was preceded by membrane depolarization of mitochondria. These results indicate that BK channel opening by NDGA in PCASMCs is due to the direct action on a subunit and also to Ca2+ release from sarcoplasmic reticulum, presumably via, at least in part, the inhibition of mitochondria respiration.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"25 1","pages":"53-63"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78366304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We investigated the effect of black currant (BC) concentrate on smooth muscle in rat thoracic aorta. BC concentrate dose-dependently relaxed the norepinephrine (0.1 microM)-precontracted aorta, and the response was abolished after endothelium removal. Both oxyhemoglobin (1 microM), a nitric oxide (NO) scavenger, and IH-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 0.5 microM), an inhibitor of guanylyl cyclase (GC), inhibited the relaxing effect of BC concentrate. NG-nitro-L-arginine methyl ester (L-NAME, 10 microM), a nitric oxide synthase (NOS) inhibitor, inhibited the relaxation, and the subsequent addition of L-arginine (1 mM), a NOS substrate, reversed the inhibitory effects of L-NAME. Neither indomethacin (10 microM), an inhibitor of cyclooxygenase, nor atropine (1 microM), an antagonist of muscarinic receptors, modified the effect of BC concentrate. Diphenhydramine (3 microM) and chlorpheniramine (2 microM), selective antagonists of H1-receptors, inhibited the relaxation, but cimetidine (0.3 mM), a selective antagonist of H2-receptors, did not affect the relaxation. These results indicate that, in the rat aorta, BC concentrate enhances synthesis of NO, which subsequently induces the endothelium-dependent vasorelaxation via the H1-receptors on the endothelium.
{"title":"Endothelium-dependent vasorelaxation induced by black currant concentrate in rat thoracic aorta.","authors":"Yuko C. Nakamura, H. Matsumoto, K. Todoki","doi":"10.1254/JJP.89.29","DOIUrl":"https://doi.org/10.1254/JJP.89.29","url":null,"abstract":"We investigated the effect of black currant (BC) concentrate on smooth muscle in rat thoracic aorta. BC concentrate dose-dependently relaxed the norepinephrine (0.1 microM)-precontracted aorta, and the response was abolished after endothelium removal. Both oxyhemoglobin (1 microM), a nitric oxide (NO) scavenger, and IH-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 0.5 microM), an inhibitor of guanylyl cyclase (GC), inhibited the relaxing effect of BC concentrate. NG-nitro-L-arginine methyl ester (L-NAME, 10 microM), a nitric oxide synthase (NOS) inhibitor, inhibited the relaxation, and the subsequent addition of L-arginine (1 mM), a NOS substrate, reversed the inhibitory effects of L-NAME. Neither indomethacin (10 microM), an inhibitor of cyclooxygenase, nor atropine (1 microM), an antagonist of muscarinic receptors, modified the effect of BC concentrate. Diphenhydramine (3 microM) and chlorpheniramine (2 microM), selective antagonists of H1-receptors, inhibited the relaxation, but cimetidine (0.3 mM), a selective antagonist of H2-receptors, did not affect the relaxation. These results indicate that, in the rat aorta, BC concentrate enhances synthesis of NO, which subsequently induces the endothelium-dependent vasorelaxation via the H1-receptors on the endothelium.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"8 1","pages":"29-35"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81575252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenteropathy is the most common among patients who use non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of inflammatory disorders. It is known that rheumatoid arthritic patients are more susceptible to NSAID-induced gastropathy than other NSAID users. This article reviewed our recent studies concerning the influence of arthritic conditions on gastric ulcerogenic response to NSAID and healing response of chronic gastric ulcers in rats. Gastric lesions induced by indomethacin, one of the conventional NSAIDs, were markedly aggravated in arthritic rats. This increased ulcerogenic response in arthritic rats was attributable to nitric oxide production due to up-regulation of inducible nitric oxide synthase. In arthritic rat stomachs, cyclooxygenase (COX)-2 was also up-regulated, where COX-2 selective inhibitors such as rofecoxib or celecoxib provoked gross lesions, although they caused no damage in normal rats. In addition, the healing of chronic gastric ulcers was also delayed in arthritic rats because of less expression of various growth factors such as basic fibroblast growth factors or insulin-like growth factors. Based on these findings, it is concluded that arthritic conditions alter the mucosal ulcerogenic and healing responses in the stomach. Especially, caution should be paid on the use of COX-2 selective inhibitors in rheumatoid arthritic patients.
{"title":"Alteration of gastric ulcerogenic and healing responses in rats with adjuvant-induced arthritis.","authors":"S. Kato, K. Takeuchi","doi":"10.1254/JJP.89.1","DOIUrl":"https://doi.org/10.1254/JJP.89.1","url":null,"abstract":"Gastroenteropathy is the most common among patients who use non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of inflammatory disorders. It is known that rheumatoid arthritic patients are more susceptible to NSAID-induced gastropathy than other NSAID users. This article reviewed our recent studies concerning the influence of arthritic conditions on gastric ulcerogenic response to NSAID and healing response of chronic gastric ulcers in rats. Gastric lesions induced by indomethacin, one of the conventional NSAIDs, were markedly aggravated in arthritic rats. This increased ulcerogenic response in arthritic rats was attributable to nitric oxide production due to up-regulation of inducible nitric oxide synthase. In arthritic rat stomachs, cyclooxygenase (COX)-2 was also up-regulated, where COX-2 selective inhibitors such as rofecoxib or celecoxib provoked gross lesions, although they caused no damage in normal rats. In addition, the healing of chronic gastric ulcers was also delayed in arthritic rats because of less expression of various growth factors such as basic fibroblast growth factors or insulin-like growth factors. Based on these findings, it is concluded that arthritic conditions alter the mucosal ulcerogenic and healing responses in the stomach. Especially, caution should be paid on the use of COX-2 selective inhibitors in rheumatoid arthritic patients.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"61 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91235578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ATP/dithiothreitol (DTT)-stimulated guanylate cyclase (GC) in lung membrane was stimulated 18-fold by ATP and DTT, and both its activity and atrial natriuretic peptide (ANP)-stimulated GC activity were observed to be additive. ATP/DTT-stimulated GC was solubilized by octyl glucoside (OG) to examine the mechanism of ATP/DTT-stimulation. GC in OG-extracts was stimulated maximally 2.5-fold by both ATP, ATPgammaS or AMPPNP, and DTT. Preincubation of OG-extracts at 10 degrees C with AMPPNP and DTT (1st-preincubation) converted GC to an insensitive state to stimulation by both ATP and DTT, and this conversion was partly inhibited by a protein phosphatase-1 inhibitor (10-1,000 nM okadaic acid). On the other hand, ANP-stimulated GC was not converted to an insensitive state to ANP/ATP-stimulation by the 1st-preincubation. Subsequent preincubation of OG-extracts at 10 degrees C with both DTT and, ATP or ATPgammaS but not AMPPNP converted GC to a state sensitive to ATP/DTT-stimulation, and this conversion was partly inhibited by inhibitors of Ca2+/calmodulin-dependent protein kinase II (KN-62 and KN-93). In contrast, the preincubation with KN-62 and KN-93 had no effect on ANP-stimulated GC activity. The results suggested that phosphorylation was involved in the regulation of ATP/DTT-stimulated GC sensitivity to ATP/DTT-stimulation and that ATP/DTT-stimulated GC activity was likely to be a different type from ANP-stimulated GC activity.
{"title":"Regulation of guanylate cyclase by ATP and dithiothreitol in rat lung membrane: involvement of an insensitive and a sensitive state to ATP/dithiothreitol-stimulation.","authors":"Shiwen Luo, M. Takano, T. Asakawa","doi":"10.1254/JJP.89.72","DOIUrl":"https://doi.org/10.1254/JJP.89.72","url":null,"abstract":"ATP/dithiothreitol (DTT)-stimulated guanylate cyclase (GC) in lung membrane was stimulated 18-fold by ATP and DTT, and both its activity and atrial natriuretic peptide (ANP)-stimulated GC activity were observed to be additive. ATP/DTT-stimulated GC was solubilized by octyl glucoside (OG) to examine the mechanism of ATP/DTT-stimulation. GC in OG-extracts was stimulated maximally 2.5-fold by both ATP, ATPgammaS or AMPPNP, and DTT. Preincubation of OG-extracts at 10 degrees C with AMPPNP and DTT (1st-preincubation) converted GC to an insensitive state to stimulation by both ATP and DTT, and this conversion was partly inhibited by a protein phosphatase-1 inhibitor (10-1,000 nM okadaic acid). On the other hand, ANP-stimulated GC was not converted to an insensitive state to ANP/ATP-stimulation by the 1st-preincubation. Subsequent preincubation of OG-extracts at 10 degrees C with both DTT and, ATP or ATPgammaS but not AMPPNP converted GC to a state sensitive to ATP/DTT-stimulation, and this conversion was partly inhibited by inhibitors of Ca2+/calmodulin-dependent protein kinase II (KN-62 and KN-93). In contrast, the preincubation with KN-62 and KN-93 had no effect on ANP-stimulated GC activity. The results suggested that phosphorylation was involved in the regulation of ATP/DTT-stimulated GC sensitivity to ATP/DTT-stimulation and that ATP/DTT-stimulated GC activity was likely to be a different type from ANP-stimulated GC activity.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"19 1","pages":"72-80"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85503948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Ohkita, M. Takaoka, Y. Shiota, Rumi Nojiri, M. Sugii, Y. Matsumura
BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-kappaB), which prevents a step of the phosphorylation of inhibitory protein IkappaB bound to NF-kappaB, suppressed basal and tumor necrosis factor (TNF)-alpha-induced prepro endothelin (ET)-1 mRNA expression and NF-kappaB activation in cultured vascular endothelial cells. BAY 11-7082 significantly decreased basal and TNF-alpha-induced ET-1 release from endothelial cells. These results indicate that the inhibition of NF-kappaB activation contributes to the suppressive effect of BAY 11-7082 on ET-1 gene expression and ET-1 release, thereby suggesting that NF-kappaB plays an important role in the regulation of ET-1 production.
BAY 11-7082是核因子- kappab (NF-kappaB)的抑制剂，可阻止IkappaB与NF-kappaB结合的抑制蛋白磷酸化，抑制培养血管内皮细胞中基底和肿瘤坏死因子(TNF)- α诱导的内皮素(ET)-1 mRNA表达和NF-kappaB活化。BAY 11-7082显著降低内皮细胞基底和tnf α诱导的ET-1释放。这些结果表明，抑制NF-kappaB激活有助于BAY 11-7082对ET-1基因表达和ET-1释放的抑制作用，从而提示NF-kappaB在调节ET-1的产生中起重要作用。
{"title":"A Nuclear Factor-κB Inhibitor BAY 11-7082 Suppresses Endothelin-1 Production in Cultured Vascular Endothelial Cells","authors":"M. Ohkita, M. Takaoka, Y. Shiota, Rumi Nojiri, M. Sugii, Y. Matsumura","doi":"10.1254/JJP.89.81","DOIUrl":"https://doi.org/10.1254/JJP.89.81","url":null,"abstract":"BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-kappaB), which prevents a step of the phosphorylation of inhibitory protein IkappaB bound to NF-kappaB, suppressed basal and tumor necrosis factor (TNF)-alpha-induced prepro endothelin (ET)-1 mRNA expression and NF-kappaB activation in cultured vascular endothelial cells. BAY 11-7082 significantly decreased basal and TNF-alpha-induced ET-1 release from endothelial cells. These results indicate that the inhibition of NF-kappaB activation contributes to the suppressive effect of BAY 11-7082 on ET-1 gene expression and ET-1 release, thereby suggesting that NF-kappaB plays an important role in the regulation of ET-1 production.","PeriodicalId":14750,"journal":{"name":"Japanese journal of pharmacology","volume":"404 1","pages":"81-84"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84859302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：