Journal of Smooth Muscle Research最新文献_第7页

Significant contribution of TRPC6 channel-mediated Ca2+ influx to the pathogenesis of Crohn's disease fibrotic stenosis TRPC6通道介导的Ca2+内流在克罗恩病纤维化狭窄发病机制中的重要贡献

Journal of Smooth Muscle Research Pub Date : 2016-11-03 DOI: 10.1540/jsmr.52.78

L. Kurahara, K. Hiraishi, M. Sumiyoshi, Mayumi Doi, Yaopeng Hu, K. Aoyagi, Yuwen Jian, R. Inoue

{"title":"Significant contribution of TRPC6 channel-mediated Ca2+ influx to the pathogenesis of Crohn's disease fibrotic stenosis","authors":"L. Kurahara, K. Hiraishi, M. Sumiyoshi, Mayumi Doi, Yaopeng Hu, K. Aoyagi, Yuwen Jian, R. Inoue","doi":"10.1540/jsmr.52.78","DOIUrl":"https://doi.org/10.1540/jsmr.52.78","url":null,"abstract":"Intestinal fibrosis is an intractable complication of Crohn's disease (CD), and, when occurring excessively, causes severe intestinal obstruction that often necessitates surgical resection. The fibrosis is characterized by an imbalance in the turnover of extracellular matrix (ECM) components, where intestinal fibroblasts/myofibroblasts play active roles in ECM production, fibrogenesis and tissue remodeling, which eventually leads to the formation of stenotic lesions. There is however a great paucity of knowledge about how intestinal fibrosis initiates and progresses, which hampers the development of effective pharmacotherapies against CD. Recently, we explored the potential implications of transient receptor potential (TRP) channels in the pathogenesis of intestinal fibrosis, since they are known to act as cellular stress sensors/transducers affecting intracellular Ca2+ homeostasis/dynamics, and are involved in a broad spectrum of cell pathophysiology including inflammation and tissue remodeling. In this review, we will place a particular emphasis on the intestinal fibroblast/myofibroblast TRPC6 channel to discuss its modulatory effects on fibrotic responses and therapeutic potential for anti-fibrotic treatment against CD-related stenosis.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"52 1","pages":"78 - 92"},"PeriodicalIF":0.0,"publicationDate":"2016-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.52.78","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67067455","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}

引用次数: 6

MYPT1 isoforms expressed in HEK293T cells are differentially phosphorylated after GTPγS treatment gtp - γ s处理后，HEK293T细胞中表达的MYPT1亚型发生了差异磷酸化

Journal of Smooth Muscle Research Pub Date : 2016-10-07 DOI: 10.1540/jsmr.52.66

Simon Lin, F. Brozovich

引用次数: 3

Resveratrol can both enhance and relax adrenergic contractions of the rat tail artery 白藜芦醇可以增强和放松大鼠尾动脉的肾上腺素能性收缩

Journal of Smooth Muscle Research Pub Date : 2016-03-02 DOI: 10.1540/jsmr.52.18

Sayra M. Stom, Laura E. Phelps, J. Peuler

{"title":"Resveratrol can both enhance and relax adrenergic contractions of the rat tail artery","authors":"Sayra M. Stom, Laura E. Phelps, J. Peuler","doi":"10.1540/jsmr.52.18","DOIUrl":"https://doi.org/10.1540/jsmr.52.18","url":null,"abstract":"Our aims were to determine 1) if resveratrol's vasorelaxant action is greater in the distal (resistance) versus proximal (conductance) portion of the rat tail artery, and 2) if it can be blocked by agents known to block different potassium (K) channels in arterial smooth muscle. We found that its half-maximally effective concentration values were essentially identical (25 ± 3 versus 27 ± 3 μM) for relaxing adrenergically-precontracted rings prepared from distal versus proximal tissues. This does not confirm a previous report of greater relaxation in resistance versus conductance arteries. We also found that its relaxation could not be blocked by any of seven different K channel blockers. However, we uncovered a novel unanticipated action not yet reported. In half our arterial ring preparations, resveratrol transiently enhanced adrenergically-induced precontractions beginning well before its sustained relaxant effect became apparent. This action provides the first reasonable explanation for previously unexplained increases in arterial pressures observed during acute intravenous administration of resveratrol to animal models of traumatic ischemic tissue injury, in which hypotension is often present and in need of correction. Also unanticipated, this same transient enhancement of adrenergic contraction was notably inhibited by some of the same K channel blockers (particularly tetraethylammonium and glibenclamide) that failed to influence its relaxant effect. Although we do not rule out smooth muscle as a possible site for such a paradoxical finding, we suspect resveratrol could also be acting on K-selective mechano-sensitive ion channels located in the endothelium where they may participate in release of contracting factors.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"52 1","pages":"18 - 35"},"PeriodicalIF":0.0,"publicationDate":"2016-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.52.18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67067314","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}

引用次数: 2

TRPA1-dependent regulation of bladder detrusor smooth muscle contractility in normal and type I diabetic rats trpa1依赖性调节正常和1型糖尿病大鼠膀胱逼尿肌平滑肌收缩

Journal of Smooth Muscle Research Pub Date : 2016-03-02 DOI: 10.1540/jsmr.52.1

I. B. Philyppov, Oksana N. Paduraru, K. Gulak, R. Skryma, N. Prevarskaya, Y. Shuba

{"title":"TRPA1-dependent regulation of bladder detrusor smooth muscle contractility in normal and type I diabetic rats","authors":"I. B. Philyppov, Oksana N. Paduraru, K. Gulak, R. Skryma, N. Prevarskaya, Y. Shuba","doi":"10.1540/jsmr.52.1","DOIUrl":"https://doi.org/10.1540/jsmr.52.1","url":null,"abstract":"TRPA1 is a Ca2+-permeable cation channel that is activated by painful low temperatures (˂17 °C), irritating chemicals, reactive metabolites and mediators of inflammation. In the bladder TRPA1 is predominantly expressed in sensory afferent nerve endings, where it mediates sensory transduction. The contractile effect of its activation on detrusor smooth muscle (DSM) is explained by the release from sensory afferents of inflammatory factors – tachykinins and prostaglandins, which cause smooth muscle cell contraction. Diabetes is a systemic disease, with common complications being diabetic cystopathies and urinary incontinence. However, data on how diabetes affects bladder contractility associated with TRPA1 activation are not available. In this study, by using a rat model with streptozotocin-induced type I diabetes, contractility measurements of DSM strips in response to TRPA1-activating and modulating pharmacological agents and assessment of TRPA1 mRNA expression in bladder-innervating dorsal root ganglia, we have shown that diabetes enhances the TRPA1-dependent mechanism involved in bladder DSM contractility. This is not due to changes in TRPA1 expression, but mainly due to the general inflammatory reaction caused by diabetes. The latter leads to an increase in cyclooxygenase-2-dependent prostaglandin synthesis through the mechanisms associated with substance P activity. This results in the enhanced functional coupling between the tachykinin and prostanoid systems, and the concomitant increase of their impact on DSM contractility in response to TRPA1 activation.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"52 1","pages":"1 - 17"},"PeriodicalIF":0.0,"publicationDate":"2016-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.52.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67067278","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}

引用次数: 14

The vascular clock system generates the intrinsic circadian rhythm of vascular contractility 血管时钟系统产生血管收缩的内在昼夜节律

Journal of Smooth Muscle Research Pub Date : 2016-03-02 DOI: 10.1540/jsmr.51.95

Toshiro Saito

引用次数: 9

Effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying evaluated using a non-invasive breath test in conscious rats. 利用无创呼吸试验评价清醒大鼠直烷基链、额外羟基化烷基链和支链氨基酸对胃排空的影响。

Journal of Smooth Muscle Research Pub Date : 2016-01-01 DOI: 10.1540/jsmr.52.36

Masayuki Uchida, Orie Kobayashi, Kaori Iwasawa, Kimiko Shimizu

{"title":"Effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying evaluated using a non-invasive breath test in conscious rats.","authors":"Masayuki Uchida, Orie Kobayashi, Kaori Iwasawa, Kimiko Shimizu","doi":"10.1540/jsmr.52.36","DOIUrl":"https://doi.org/10.1540/jsmr.52.36","url":null,"abstract":"Aim: Some amino acids been known to influence gastric emptying. Thus we have evaluated the effects of straight alkyl chain, extra hydroxylated alkyl chain and branched chain amino acids on gastric emptying.Materials and methods: Gastric emptying was evaluated in rats after feeding with Racol (nutrient formulae) containing [1-(13)C] acetic acid. Using a breath test, the content of (13)CO2 in their expired air was measured by infrared analyzers. Rats were orally administered with test amino acids, while control rats were administered orally with distilled water.Results: The expired (13)CO2 content in the expired air increased with time, peaked after about 30 min and decreased thereafter. Among the amino acids having an alkyl chain, L-serine, L-alanine and L-glycine, significantly decreased the (13)CO2 content and Cmax, and delayed Tmax, suggesting inhibition and delay of gastric emptying. AUC(120min) values of L-alanine and L-glycine also decreased significantly. L-Threonine significantly decreased (13)CO2 content and delayed Tmax, but had no influence on Cmax and AUC(120min) values, suggesting a delay of gastric emptying. L-Isoleucine and L-leucine and L-valine significantly decreased (13)CO2 content, suggesting inhibition of the gastric emptying, but Cmax, Tmax and AUC(120min) values were not significantly affected.Conclusion: The results show that the amino acids used in the present study had different effects on gastric emptying. Moreover, it was found that inhibition and delay of gastric emptying were clearly classifiable by analyzing the change in (13)CO2 content of the expired air and the Cmax, Tmax and AUC(120min) values.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"52 ","pages":"36-44"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.52.36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34476264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Highly sensitive myosin phosphorylation analysis in the renal afferent arteriole. 肾传入小动脉高度敏感肌球蛋白磷酸化分析。

Journal of Smooth Muscle Research Pub Date : 2016-01-01 DOI: 10.1540/jsmr.52.45

Kosuke Takeya

{"title":"Highly sensitive myosin phosphorylation analysis in the renal afferent arteriole.","authors":"Kosuke Takeya","doi":"10.1540/jsmr.52.45","DOIUrl":"https://doi.org/10.1540/jsmr.52.45","url":null,"abstract":"The regulation of smooth muscle contraction and relaxation involves phosphorylation and dephosphorylation of regulatory proteins, particularly myosin. To elucidate the regulatory mechanisms, analyzing the phosphorylation signal transduction is crucial. Although a pharmacological approach with selective inhibitors is sensitive and a useful technique, it leads to speculation regarding a signaling pathway but does not provide direct evidence of changes at a molecular level. We developed a highly sensitive biochemical technique to analyze phosphorylation by adapting Phos-tag SDS-PAGE. With this technique, we successfully analyzed myosin light chain (LC20) phosphorylation in tiny renal afferent arterioles. In the rat afferent arterioles, endothelin-1 (ET-1) induced diphosphorylation of LC20 at Ser19 and Thr18 as well as monophosphorylation at Ser19 via ET <symbol>B</symbol> receptor activation. Considering that LC20 diphosphorylation can decrease the rate of dephosphorylation and thus relaxation, we concluded that LC20 diphosphorylation contributes, at least in part, to the prolonged contraction induced by ET-1 in the renal afferent arteriole.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"52 0","pages":"45-55"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.52.45","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34698106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Influence of amino acids on gastric adaptive relaxation (accommodation) in rats as evaluated with a barostat. 氨基酸对大鼠胃适应性松弛(调节)的影响。

Journal of Smooth Muscle Research Pub Date : 2016-01-01 DOI: 10.1540/jsmr.52.56

Masayuki Uchida, Chizuru Iwamoto

{"title":"Influence of amino acids on gastric adaptive relaxation (accommodation) in rats as evaluated with a barostat.","authors":"Masayuki Uchida, Chizuru Iwamoto","doi":"10.1540/jsmr.52.56","DOIUrl":"https://doi.org/10.1540/jsmr.52.56","url":null,"abstract":"Aim: The present study aimed to evaluate the effects of selected straight alkyl chain, hydroxylated chain and branched chain amino acids on gastric adaptive relaxation, as these have previously been shown to have differing effects on gastric emptying.Materials and methods: Gastric adaptive relaxation was evaluated using a barostat in rats under urethane anesthesia. The pressure within the balloon, introduced from the mouth to the stomach, was changed stepwise from 1 to 8 mmHg. The increased volume just after the increase of balloon pressure was defined as distension-induced gastric adaptive relaxation (accommodation). Amino acids were administered orally or intravenously.Results: As compared with control rats administered with distilled water, those rats that were orally administered amino acids having straight alkyl chain and extra hydroxylated alkyl chain, such as glycine and l-serine, had significantly enhanced gastric adaptive relaxation, but administration of l-alanine and l-threonine did not. Branched chain amino acids, such as l-isoleucine, l-leucine and l-valine, also did not significantly influence gastric adaptive relaxation. Glycine and l-serine showed the same efficacy when administered intravenously.Conclusion: Among the amino acids evaluated in the present study, glycine and l-serine significantly enhanced gastric adaptive relaxation, suggesting that short alkyl chain amino acids may enhance gastric adaptive relaxation as compared with the other amino acids. These findings may suggest that glycine and l-serine would be useful in the therapy of functional dyspepsia, especially for early satiety, because the dysfunction of adaptive relaxation is one of the causes of early satiety.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"52 0","pages":"56-65"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.52.56","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34334226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Activation of 5-HT4 receptors facilitates neurogenesis of injured enteric neurons at an anastomosis in the lower gut 5-HT4受体的激活促进了下肠吻合处损伤的肠神经元的神经发生

Journal of Smooth Muscle Research Pub Date : 2015-12-09 DOI: 10.1540/jsmr.51.82

M. Takaki, Kei Goto, Isao Kawahara, J. Nabekura

{"title":"Activation of 5-HT4 receptors facilitates neurogenesis of injured enteric neurons at an anastomosis in the lower gut","authors":"M. Takaki, Kei Goto, Isao Kawahara, J. Nabekura","doi":"10.1540/jsmr.51.82","DOIUrl":"https://doi.org/10.1540/jsmr.51.82","url":null,"abstract":"Two-photon microscopy (2PM) can enable high-resolution deep imaging of thick tissue by exciting a fluorescent dye and protein at anastomotic sites in the mouse small intestine in vivo. We performed gut surgery and transplanted neural stem cells (NSC) from the embryonic central nervous system after marking them with the fluorescent cell linker, PKH26. We found that neurons differentiated from transplanted NSC (PKH [+]) and newborn enteric neurons differentiated from mobilized (host) NSC (YFP [+]) could be localized within the granulation tissue of anastomoses. A 5-HT4-receptor agonist, mosapride citrate (MOS), significantly increased the number of PKH (+) and YFP (+) neurons by 2.5-fold (P<0.005). The distribution patterns of PKH (+) neurons were similar to those of YFP (+) neurons. On the other hand, the 5-HT4-receptor antagonist, SB-207266 abolished these effects of MOS. These results indicate that neurogenesis from transplanted NSC is facilitated by activation of 5-HT4-receptors. Thus, a combination of drug administration and cell transplantation could be more beneficial than exclusive cell transplantation in treating Hirschsprung's disease and related disorders including post rectal cancer surgery. The underlying mechanisms for its action were explored using immunohistochemistry of the longitudinal mouse ileum and rat rectal preparations including an anastomosis. MOS significantly increased the number of new neurons, but not when co-administered with either of a protein tyrosine kinase receptor, c-RET two inhibitors. The c-RET signaling pathway contributes to enteric neurogenesis facilitated by MOS. In the future, we would perform functional studies of new neurons over the thick granulation tissue at anastomoses, using in vivo imaging with 2PM and double transgenic mice expressing a calcium indicator such as GCaMP6 and channelrhodopsin.","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"51 1","pages":"82 - 94"},"PeriodicalIF":0.0,"publicationDate":"2015-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.51.82","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67067194","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}

引用次数: 11

Ca2+ dependent but PKC independent signalling mediates UTP induced contraction of rat mesenteric arteries. Ca2+依赖但PKC独立的信号介导UTP诱导的大鼠肠系膜动脉收缩。

Journal of Smooth Muscle Research Pub Date : 2015-01-01 DOI: 10.1540/jsmr.51.58

Fouzia Panhwar, Richard D Rainbow, Robert Jackson, Noel W Davies

{"title":"Ca2+ dependent but PKC independent signalling mediates UTP induced contraction of rat mesenteric arteries.","authors":"Fouzia Panhwar, Richard D Rainbow, Robert Jackson, Noel W Davies","doi":"10.1540/jsmr.51.58","DOIUrl":"https://doi.org/10.1540/jsmr.51.58","url":null,"abstract":"Uridine triphosphate (UTP) can be released from damaged cells to cause vasoconstriction. Although UTP is known to act through P2Y receptors and PLC activation in vascular smooth muscle, the role of PKC in generating the response is somewhat unclear. Here we have used Tat-linked membrane permeable peptide inhibitors of PKC to assess the general role of PKC and also of specific isoforms of PKC in the UTP induced contraction of rat mesenteric artery. We examined the effect of PKC inhibition on UTP induced contraction, increased cytoplasmic Ca(2+) and reduction of K(+) currents and found that PKC inhibition caused a relatively small attenuation of contraction but had little effect on changes in cytoplasmic Ca(2+). UTP attenuation of both voltage-gated (Kv) and ATP-dependent (KATP) K(+) currents was abolished when intracellular Ca(2+) was decreased from 100 to 20 nM. PKC inhibition reduced slightly the ability of UTP to attenuate Kv currents but had no effect on KATP current inhibition. In conclusion, both UTP induced contraction of mesenteric artery and the inhibition of Kv and KATP currents of mesenteric artery smooth muscle cells by UTP are relatively independent of PKC activation; furthermore, the inhibition of both Kv and KATP currents requires intracellular Ca(2+). ","PeriodicalId":39619,"journal":{"name":"Journal of Smooth Muscle Research","volume":"51 ","pages":"58-69"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1540/jsmr.51.58","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34070601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1