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Gastric emptying after artificial ulceration in rats: differences due to the site of the ulcer and the effects of prokinetic drugs. 大鼠人工溃疡后胃排空:溃疡部位及促胃动力药物作用的差异。
Q3 Medicine Pub Date : 2017-01-01 DOI: 10.1540/jsmr.53.48
Masayuki Uchida, Orie Kobayashi, Kimiko Shimizu

Background This study aimed to evaluate the effects of the position of an acetic acid-induced gastric ulcer and the effects of prokinetic drugs on gastric emptying. Materials and Methods Male Sprague-Dawley rats were used in this study. Acetic acid ulcers were induced either in the region between the fundus and pylorus on the anterior wall of the stomach or in the glandular region on the greater curvature of the stomach to determine whether there were regional differences in the effect of the ulcers. Gastric emptying was evaluated with a breath test using [1-13C] acetic acid. In addition, the effects of the prokinetic drugs, metoclopramide and mosapride, on gastric emptying were also evaluated. Results Acetic acid induced ulcers in the region between the fundus and pylorus on the anterior wall of the stomach significantly delayed gastric emptying as compared with control rats, but not the acetic acid induced ulcers in the glandular region on the greater curvature of the stomach. Metoclopramide and mosapride did not improve the delayed gastric emptying even at doses that enhanced gastric emptying in normal rats. Conclusion These findings show that gastric emptying is influenced by the position of the ulcer and the region between the fundus and pylorus on the anterior wall plays an important role in gastric emptying. Moreover, it was found that metoclopramide and mosapride do not improve the delayed gastric emptying caused by acetic acid ulcers induced on the anterior wall in the region between the fundus and pylorus.

本研究旨在探讨醋酸性胃溃疡发生位置的影响及促动力学药物对胃排空的影响。材料与方法采用雄性Sprague-Dawley大鼠。在胃前壁底部和幽门之间的区域或胃大弯曲的腺体区域诱发醋酸溃疡,以确定溃疡的效果是否存在区域差异。胃排空用[1-13C]乙酸呼气试验评估。此外,还评价了促动力学药物甲氧氯普胺和莫沙必利对胃排空的影响。结果与对照组相比,胃前壁底部-幽门间区醋酸诱发的溃疡明显延迟了胃排空,而胃大弯曲处的腺区乙酸诱发的溃疡没有明显延迟。甲氧氯普胺和莫沙必利即使在增强正常大鼠胃排空的剂量下也不能改善胃排空延迟。结论胃排空受溃疡位置的影响,胃底与幽门前壁之间的区域在胃排空中起重要作用。此外,我们发现甲氧氯普胺和莫沙必利并不能改善胃底和幽门之间区域前壁醋酸溃疡引起的胃排空延迟。
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引用次数: 2
Deterioration of epithelium mediated mechanisms in diabetic-antigen sensitized airways of guinea pigs 豚鼠糖尿病抗原致敏气道中上皮介导的恶化机制
Q3 Medicine Pub Date : 2016-12-27 DOI: 10.1540/jsmr.52.93
S. Bano, Omanwar Swati, Muralidhar Kambadur, F. Mohammad
Background The onset of diabetes causes disruption of respiratory epithelial mediators. The present study investigates whether diabetes modifies the epithelium mediated bronchial responses in hyper-reactive airway smooth muscle (ASM) primarily through nitric oxide (NO), cyclooxygenase (COX), and epithelium derived hyperpolarizing factor (EpDHF) pathways. Methods Experimental model of guinea pigs having hyper-reactive airways with or without diabetes were developed. The responses of tracheal rings to cumulative concentrations of acetylcholine (ACh) and isoproterenol (IP) in the presence and absence of epithelium and before and after incubation with NO, K+ATP and COX inhibitors, N-(ω)-Nitro-L-arginine methyl ester (L-NAME; 100 µM), glybenclamide (10 µM) and indomethacin (100 µM) were assessed. Results In diabetic guinea pigs with hyper-reactive airways, a decrease in ACh induced bronchoconstriction was observed after epithelium removal and after incubation with L-NAME/indomethacin, suggesting damage to NO/COX pathways. Hyper-reactivity did not alter the response of trachea to ACh but affected the response to IP which was further reduced in hyper-reactive animals with diabetes. The ASM response to IP after glybenclamide treatment did not alter in hyper-reactive guinea pigs and diabetic guinea pigs with hyper-reactive airways, suggesting damage to the EpDHF pathway. Treatment with indomethacin reduced IP response in the hyper-reactive model, and did not produce any change in diabetic model with hyper-reactive airways, indicating further disruption of the COX pathway. Conclusion EpDHF pathway is damaged in hyper-reactive guinea pigs and in diabetic guinea pigs with hyper-reactive airways. Diabetes further aggravates the NO and COX mediated pathways in diabetic guinea pigs with hyper-reactive airways.
糖尿病的发病会导致呼吸上皮介质的破坏。本研究探讨糖尿病是否主要通过一氧化氮(NO)、环氧合酶(COX)和上皮源性超极化因子(EpDHF)途径改变气道平滑肌(ASM)中上皮介导的支气管反应。方法建立伴有或不伴有糖尿病的高反应性气道豚鼠实验模型。NO、K+ATP和COX抑制剂、N-(ω)-硝基- l -精氨酸甲酯(L-NAME)孵育前后气管环对乙酰胆碱(ACh)和异丙肾上腺素(IP)累积浓度的反应;100µM)、格列苯脲(10µM)和吲哚美辛(100µM)。结果在高反应性气道的糖尿病豚鼠中,去除上皮和L-NAME/吲哚美辛孵育后,观察到乙酰胆碱引起的支气管收缩减少,提示NO/COX通路受损。高反应性没有改变气管对乙酰胆碱的反应,但影响了对乙酰胆碱的反应,糖尿病高反应性动物的反应进一步降低。在高反应性豚鼠和具有高反应性气道的糖尿病豚鼠中,格列本脲治疗后对IP的ASM反应没有改变,提示EpDHF通路受损。吲哚美辛治疗降低了高反应模型的IP反应,而在高反应气道的糖尿病模型中未产生任何变化,表明COX通路进一步被破坏。结论EpDHF通路在高反应性豚鼠和伴有高反应性气道的糖尿病豚鼠中存在损伤。糖尿病进一步加重气道高反应性糖尿病豚鼠的NO和COX介导通路。
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引用次数: 2
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
Q3 Medicine 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
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.
肠纤维化是克罗恩病(CD)的一种难治性并发症,当过度发生时,会导致严重的肠梗阻,通常需要手术切除。纤维化的特点是细胞外基质(ECM)成分的周转不平衡,其中肠成纤维细胞/肌成纤维细胞在ECM的产生、纤维形成和组织重塑中发挥积极作用,最终导致狭窄病变的形成。然而,关于肠纤维化如何开始和发展的知识非常缺乏,这阻碍了有效药物治疗CD的发展。最近,我们探索了瞬时受体电位(TRP)通道在肠纤维化发病机制中的潜在意义,因为它们被认为是影响细胞内Ca2+稳态/动力学的细胞应激传感器/传感器。并且参与了广泛的细胞病理生理学,包括炎症和组织重塑。在这篇综述中,我们将特别强调肠成纤维细胞/肌成纤维细胞TRPC6通道,讨论其对纤维化反应的调节作用以及抗纤维化治疗cd相关狭窄的治疗潜力。
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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
Q3 Medicine Pub Date : 2016-10-07 DOI: 10.1540/jsmr.52.66
Simon Lin, F. Brozovich
Agonist stimulation of smooth muscle is known to activate RhoA/Rho kinase signaling, and Rho kinase phosphorylates the myosin targeting subunit (MYPT1) of myosin light chain (MLC) phosphatase at Thr696 and Thr853, which inhibits the activity of MLC phosphatase to produce a Ca2+ independent increase in MLC phosphorylation and force (Ca2+ sensitization). Alternative mRNA splicing produces four MYPT1 isoforms, which differ by the presence or absence of a central insert (CI) and leucine zipper (LZ). This study was designed to determine if Rho kinase differentially phosphorylates MYPT1 isoforms. In HEK293T cells expressing each of the four MYPT1 isoforms, we could not detect a change in Thr853 MYPT1 phosphorylation following GTPγS treatment. However, there is differential phosphorylation of MYPT1 isoforms at Thr696; GTPγS treatment increases MYPT1 phosphorylation for the CI+LZ- and CI-LZ- MYPT1 isoforms, but not the CI+LZ+ or CI-LZ+ MYPT1 isoforms. These data could suggest that in smooth muscle Rho kinase differentially phosphorylates MYPT1 isoforms.
已知平滑肌激动剂刺激可激活RhoA/Rho激酶信号,Rho激酶磷酸化myosin轻链(MLC)磷酸酶的Thr696和Thr853位点的myosin靶向亚基(MYPT1),从而抑制MLC磷酸酶的活性,产生Ca2+独立的MLC磷酸化和力(Ca2+敏化)的增加。可选择的mRNA剪接产生四种MYPT1亚型,其不同之处在于中心插入(CI)和亮氨酸拉链(LZ)的存在或缺失。本研究旨在确定Rho激酶是否会使MYPT1亚型发生差异磷酸化。在表达四种MYPT1亚型的HEK293T细胞中,我们没有检测到GTPγS处理后Thr853 MYPT1磷酸化的变化。然而,在Thr696位点存在MYPT1亚型的不同磷酸化;GTPγS处理增加了CI+LZ-和CI-LZ- MYPT1亚型的MYPT1磷酸化,但没有增加CI+LZ+或CI-LZ+ MYPT1亚型的磷酸化。这些数据可能表明,在平滑肌中,Rho激酶对MYPT1亚型的磷酸化存在差异。
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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
Q3 Medicine Pub Date : 2016-03-02 DOI: 10.1540/jsmr.52.18
Sayra M. Stom, Laura E. Phelps, J. Peuler
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.
我们的目的是确定1)白藜芦醇的血管松弛作用在大鼠尾动脉的远端(阻力)和近端(传导)部分是否更大,以及2)是否可以被已知的阻断动脉平滑肌中不同钾(K)通道的药物阻断。我们发现其半最大有效浓度值基本相同(25±3 μM vs 27±3 μM),用于放松远端和近端组织制备的肾上腺素能预收缩环。这并不能证实先前关于阻力动脉比传导动脉更松弛的报道。我们还发现它的弛豫不能被七种不同的K通道阻滞剂中的任何一种阻断。然而,我们发现了一个尚未报道的意想不到的新行动。在我们一半的动脉环制剂中,白藜芦醇在其持续的松弛作用变得明显之前就开始短暂地增强肾上腺素能诱导的预收缩。这一作用为创伤性缺血性组织损伤动物模型急性静脉注射白藜芦醇时观察到的动脉压升高提供了第一个合理的解释,在这种情况下经常出现低血压,需要纠正。同样出乎意料的是,某些K通道阻滞剂(尤其是四乙基铵和格列本脲)明显抑制了肾上腺素能收缩的短暂性增强,而这些阻滞剂未能影响其松弛作用。尽管我们不排除平滑肌是这种矛盾发现的可能部位,但我们怀疑白藜芦醇也可能作用于位于内皮中的k -选择性机械敏感离子通道,在那里它们可能参与收缩因子的释放。
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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
Q3 Medicine 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
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.
TRPA1是一种Ca2+渗透性阳离子通道,它被令人痛苦的低温(小于17°C)、刺激性化学物质、反应性代谢物和炎症介质激活。在膀胱中,TRPA1主要表达于感觉传入神经末梢,介导感觉传导。其激活对逼尿肌平滑肌(DSM)的收缩作用可以解释为炎症因子-快激肽和前列腺素的感觉传入释放,引起平滑肌细胞收缩。糖尿病是一种全身性疾病,常见的并发症是糖尿病性膀胱病变和尿失禁。然而,关于糖尿病如何影响与TRPA1激活相关的膀胱收缩性的数据尚无。在本研究中,我们利用链脲霉素诱导的1型糖尿病大鼠模型,测量了DSM条在TRPA1激活和调节药物作用下的收缩性,并评估了膀胱神经支配背根神经节中TRPA1 mRNA的表达,结果表明糖尿病增强了膀胱DSM收缩性的TRPA1依赖机制。这不是由于TRPA1表达的改变,而主要是由于糖尿病引起的一般炎症反应。后者通过与P物质活性相关的机制导致环氧化酶-2依赖性前列腺素合成的增加。这导致快速激肽和前列腺素系统之间的功能耦合增强,以及它们对响应TRPA1激活的DSM收缩性的影响随之增加。
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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
Q3 Medicine Pub Date : 2016-03-02 DOI: 10.1540/jsmr.51.95
Toshiro Saito
Many of the cardiovascular parameters or incidences of coronary artery diseases display circadian variations. These day/night time variances may be attributable to the diurnal change in vascular contractility. However, the molecular mechanism of the vascular clock system which generates the circadian variation of vascular contractility has remained largely unknown. Recently we found the existence of the intrinsic circadian rhythm in vascular contractility. A clock gene Rorα in vascular smooth muscle cells (VSMC) provokes the diurnal oscillatory change in the expression of Rho-associated kinase 2 (ROCK2), which induces the time-of-day-dependent variation in the agonist-induced phosphorylation of myosin light chain (MLC) and myofilament Ca2+ sensitization. In this review, we introduce our recent findings with reference to the molecular basis of the biological clock system and the current literature concerning cardiovascular chronobiology.
许多心血管参数或冠状动脉疾病的发病率显示昼夜变化。这些昼夜时间差异可能归因于血管收缩能力的日变化。然而,产生血管收缩性昼夜变化的血管时钟系统的分子机制在很大程度上仍然未知。最近我们发现血管收缩存在内在的昼夜节律。血管平滑肌细胞(VSMC)中的时钟基因Rorα引起rho相关激酶2 (ROCK2)表达的昼夜振荡变化,从而诱导激动剂诱导的肌球蛋白轻链(MLC)磷酸化和肌丝Ca2+敏化的时间依赖性变化。本文就生物钟系统的分子基础和心血管时间生物学的最新研究进展作一综述。
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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。
Q3 Medicine Pub Date : 2016-01-01 DOI: 10.1540/jsmr.52.36
Masayuki Uchida, Orie Kobayashi, Kaori Iwasawa, Kimiko Shimizu

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.

目的:已知一些氨基酸影响胃排空。因此,我们评价了直烷基链、额外羟基化烷基链和支链氨基酸对胃排空的影响。材料与方法:用含有[1-(13)C]乙酸的Racol(营养配方)喂养大鼠,观察其胃排空情况。使用呼吸测试,用红外分析仪测量他们呼出的空气中的二氧化碳含量。大鼠口服试验氨基酸,对照组大鼠口服蒸馏水。结果:过期空气中CO2含量随时间增加而增加,约30 min后达到峰值,随后逐渐下降。在具有烷基链的氨基酸中,l -丝氨酸、l -丙氨酸和l -甘氨酸显著降低了(13)CO2含量和Cmax,并延迟了Tmax,表明抑制和延迟了胃排空。l -丙氨酸和l -甘氨酸的AUC(120min)值也显著降低。l -苏氨酸显著降低(13)CO2含量和延迟Tmax,但对Cmax和AUC(120min)值没有影响,提示胃排空延迟。l -异亮氨酸、l -亮氨酸和l -缬氨酸显著降低了(13)CO2含量,表明抑制了胃排空,但Cmax、Tmax和AUC(120min)值未受显著影响。结论:本研究中所使用的氨基酸对胃排空有不同的作用。此外,通过分析过期空气(13)CO2含量的变化以及Cmax、Tmax和AUC(120min)值的变化,可以清楚地区分胃排空的抑制和延迟。
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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。
Q3 Medicine Pub Date : 2016-01-01 DOI: 10.1540/jsmr.52.45
Kosuke Takeya

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 B 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.

平滑肌收缩和舒张的调节涉及调节蛋白的磷酸化和去磷酸化,特别是肌球蛋白。为了阐明调控机制,分析磷酸化信号转导是至关重要的。尽管选择性抑制剂的药理学方法是一种敏感和有用的技术,但它导致了对信号通路的猜测,但不能提供分子水平变化的直接证据。我们开发了一种高灵敏度的生化技术,通过适应phos标签SDS-PAGE来分析磷酸化。利用这种技术,我们成功地分析了微小肾传入小动脉中肌球蛋白轻链(LC20)的磷酸化。在大鼠传入小动脉中,内皮素-1 (ET-1)通过ET B受体激活诱导LC20在Ser19和Thr18位点的二磷酸化以及Ser19位点的单磷酸化。考虑到LC20二磷酸化可以降低去磷酸化的速率,从而导致舒张,我们得出结论,LC20二磷酸化至少在一定程度上有助于ET-1在肾传入小动脉中引起的延长收缩。
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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。
Q3 Medicine Pub Date : 2016-01-01 DOI: 10.1540/jsmr.52.56
Masayuki Uchida, Chizuru Iwamoto

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.

目的:本研究旨在评估选定的直烷基链、羟基化链和支链氨基酸对胃适应性松弛的影响,因为这些氨基酸对胃排空有不同的影响。材料与方法:用恒压器观察氨基甲酸乙酯麻醉大鼠胃适应性松弛。从口腔到胃的球囊内的压力逐步从1到8 mmHg变化。球囊压力增加后体积增加定义为胃膨胀性适应性松弛(调节)。氨基酸被口服或静脉注射。结果:与蒸馏水对照大鼠相比,口服甘氨酸、丝氨酸等具有直烷基链和额外羟基化烷基链的氨基酸可显著增强胃适应性松弛,而l-丙氨酸、l-苏氨酸则无此作用。支链氨基酸如l-异亮氨酸、l-亮氨酸和l-缬氨酸对胃适应性松弛也无显著影响。甘氨酸和l-丝氨酸在静脉注射时表现出相同的疗效。结论:在本研究评价的氨基酸中,甘氨酸和l-丝氨酸显著增强胃适应性舒张,提示短烷基链氨基酸与其他氨基酸相比可能增强胃适应性舒张。这些发现可能表明甘氨酸和l-丝氨酸在功能性消化不良的治疗中是有用的,特别是对于早期饱腹感,因为适应性放松功能障碍是早期饱腹感的原因之一。
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引用次数: 2
期刊
Journal of Smooth Muscle Research
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