The Experts below are selected from a list of 7179 Experts worldwide ranked by ideXlab platform
Miwa Misawa - One of the best experts on this subject based on the ideXlab platform.
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interleukin 13 augments bronchial Smooth Muscle Contractility with an up regulation of rhoa protein
American Journal of Respiratory Cell and Molecular Biology, 2009Co-Authors: Yoshihiko Chiba, Shuji Nakazawa, Michiko Todoroki, Koji Shinozaki, Hiroyasu Sakai, Miwa MisawaAbstract:Interleukin-13 (IL-13) is one of the central mediators for development of airway hyperresponsiveness in asthma. However, its effect on bronchial Smooth Muscle (BSM) is not well known. Recent studies revealed an involvement of RhoA/Rho-kinase in BSM contraction, and this pathway has now been proposed as a new target for asthma therapy. To elucidate the role of IL-13 on the induction of BSM hyperresponsiveness, effects of IL-13 on Contractility and RhoA expression in BSMs were investigated. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin antigen. In the repeatedly antigen-challenged mice, marked airway inflammation and BSM hyperresponsiveness with an up-regulation of IL-13 in bronchoalveolar lavage fluids were observed. In cultured human BSM cells, IL-13 caused an up-regulation of RhoA. The IL-13–induced up-regulation of RhoA was inhibited by leflunomide, an inhibitor of signal transducer and activator of transcription 6 (STAT6). In isolated BSM tissues of naive mice, the contracti...
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effect of cigarette smoke exposure in vivo on bronchial Smooth Muscle Contractility in vitro in rats
American Journal of Respiratory Cell and Molecular Biology, 2005Co-Authors: Yoshihiko Chiba, Hiroyasu Sakai, Masahiko Murata, Hiroko Ushikubo, Yuji Yoshikawa, Akiyoshi Saitoh, Junzo Kamei, Miwa MisawaAbstract:Cigarette smoking is a risk factor for the development of airway hyperresponsiveness and chronic obstructive pulmonary disease. Little is known concerning the effect of cigarette smoking on the Contractility of airway Smooth Muscle. The current study was performed to determine the responsiveness of bronchial Smooth Muscles isolated from rats that were subacutely exposed to mainstream cigarette smoke in vivo. Male Wistar rats were exposed to diluted mainstream cigarette smoke for 2 h/d every day for 2 wk. Twenty-four hours after the last cigarette smoke exposure, a marked airway inflammation (i.e., increases in numbers of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and peribronchial tissues) was observed. In these subacutely cigarette smoke-exposed animals, the responsiveness of isolated intact (nonpermeabilized) bronchial Smooth Muscle to acetylcholine, but not to high K+ -depolarization, was significantly augmented when compared with the air-exposed control group. In alpha-toxin-permeabilized bronchial Smooth Muscle strips, the acetylcholine-induced Ca2+ sensitization of contraction was significantly augmented in rats exposed to cigarette smoke, although the contraction induced by Ca2+ was control level. Immunoblot analyses revealed an increased expression of RhoA protein in the bronchial Smooth Muscle of rats that were exposed to cigarette smoke. Taken together, these findings suggest that the augmented agonist-induced, RhoA-mediated Ca2+ sensitization may be responsible for the enhanced bronchial Smooth Muscle contraction induced by cigarette smoking, which has relevance to airway hyperresponsiveness in patients with chronic obstructive pulmonary disease.
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augmented acetylcholine induced rho mediated ca2 sensitization of bronchial Smooth Muscle contraction in antigen induced airway hyperresponsive rats
British Journal of Pharmacology, 1999Co-Authors: Yoshihiko Chiba, Yuka Takada, Shigeki Miyamoto, Minori Mitsuisaito, Hideaki Karaki, Miwa MisawaAbstract:Treatment with acetylcholine (ACh) of a β-escin-permeabilized intrapulmonary bronchial Smooth Muscle of the rat induced force when the Ca2+ concentration was clamped at 1 μM. The ACh-induced Ca2+ sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivator of Rho family of proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was significantly increased in the airway hyperresponsive rats. Thus, increased airway Smooth Muscle Contractility observed in asthmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments. British Journal of Pharmacology (1999) 127, 597–600; doi:10.1038/sj.bjp.0702585
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augmented acetylcholine induced rho mediated ca2 sensitization of bronchial Smooth Muscle contraction in antigen induced airway hyperresponsive rats
British Journal of Pharmacology, 1999Co-Authors: Yoshihiko Chiba, Yuka Takada, Shigeki Miyamoto, Minori Mitsuisaito, Hideaki Karaki, Miwa MisawaAbstract:Treatment with acetylcholine (ACh) of a beta-escin-permeabilized intrapulmonary bronchial Smooth Muscle of the rat induced force when the Ca2+ concentration was clamped at 1 microM. The ACh-induced Ca2+ sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivator of Rho family of proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was significantly increased in the airway hyperresponsive rats. Thus, increased airway Smooth Muscle Contractility observed in asthmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments.
Yoshihiko Chiba - One of the best experts on this subject based on the ideXlab platform.
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interleukin 13 augments bronchial Smooth Muscle Contractility with an up regulation of rhoa protein
American Journal of Respiratory Cell and Molecular Biology, 2009Co-Authors: Yoshihiko Chiba, Shuji Nakazawa, Michiko Todoroki, Koji Shinozaki, Hiroyasu Sakai, Miwa MisawaAbstract:Interleukin-13 (IL-13) is one of the central mediators for development of airway hyperresponsiveness in asthma. However, its effect on bronchial Smooth Muscle (BSM) is not well known. Recent studies revealed an involvement of RhoA/Rho-kinase in BSM contraction, and this pathway has now been proposed as a new target for asthma therapy. To elucidate the role of IL-13 on the induction of BSM hyperresponsiveness, effects of IL-13 on Contractility and RhoA expression in BSMs were investigated. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin antigen. In the repeatedly antigen-challenged mice, marked airway inflammation and BSM hyperresponsiveness with an up-regulation of IL-13 in bronchoalveolar lavage fluids were observed. In cultured human BSM cells, IL-13 caused an up-regulation of RhoA. The IL-13–induced up-regulation of RhoA was inhibited by leflunomide, an inhibitor of signal transducer and activator of transcription 6 (STAT6). In isolated BSM tissues of naive mice, the contracti...
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effect of cigarette smoke exposure in vivo on bronchial Smooth Muscle Contractility in vitro in rats
American Journal of Respiratory Cell and Molecular Biology, 2005Co-Authors: Yoshihiko Chiba, Hiroyasu Sakai, Masahiko Murata, Hiroko Ushikubo, Yuji Yoshikawa, Akiyoshi Saitoh, Junzo Kamei, Miwa MisawaAbstract:Cigarette smoking is a risk factor for the development of airway hyperresponsiveness and chronic obstructive pulmonary disease. Little is known concerning the effect of cigarette smoking on the Contractility of airway Smooth Muscle. The current study was performed to determine the responsiveness of bronchial Smooth Muscles isolated from rats that were subacutely exposed to mainstream cigarette smoke in vivo. Male Wistar rats were exposed to diluted mainstream cigarette smoke for 2 h/d every day for 2 wk. Twenty-four hours after the last cigarette smoke exposure, a marked airway inflammation (i.e., increases in numbers of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and peribronchial tissues) was observed. In these subacutely cigarette smoke-exposed animals, the responsiveness of isolated intact (nonpermeabilized) bronchial Smooth Muscle to acetylcholine, but not to high K+ -depolarization, was significantly augmented when compared with the air-exposed control group. In alpha-toxin-permeabilized bronchial Smooth Muscle strips, the acetylcholine-induced Ca2+ sensitization of contraction was significantly augmented in rats exposed to cigarette smoke, although the contraction induced by Ca2+ was control level. Immunoblot analyses revealed an increased expression of RhoA protein in the bronchial Smooth Muscle of rats that were exposed to cigarette smoke. Taken together, these findings suggest that the augmented agonist-induced, RhoA-mediated Ca2+ sensitization may be responsible for the enhanced bronchial Smooth Muscle contraction induced by cigarette smoking, which has relevance to airway hyperresponsiveness in patients with chronic obstructive pulmonary disease.
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augmented acetylcholine induced rho mediated ca2 sensitization of bronchial Smooth Muscle contraction in antigen induced airway hyperresponsive rats
British Journal of Pharmacology, 1999Co-Authors: Yoshihiko Chiba, Yuka Takada, Shigeki Miyamoto, Minori Mitsuisaito, Hideaki Karaki, Miwa MisawaAbstract:Treatment with acetylcholine (ACh) of a β-escin-permeabilized intrapulmonary bronchial Smooth Muscle of the rat induced force when the Ca2+ concentration was clamped at 1 μM. The ACh-induced Ca2+ sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivator of Rho family of proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was significantly increased in the airway hyperresponsive rats. Thus, increased airway Smooth Muscle Contractility observed in asthmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments. British Journal of Pharmacology (1999) 127, 597–600; doi:10.1038/sj.bjp.0702585
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augmented acetylcholine induced rho mediated ca2 sensitization of bronchial Smooth Muscle contraction in antigen induced airway hyperresponsive rats
British Journal of Pharmacology, 1999Co-Authors: Yoshihiko Chiba, Yuka Takada, Shigeki Miyamoto, Minori Mitsuisaito, Hideaki Karaki, Miwa MisawaAbstract:Treatment with acetylcholine (ACh) of a beta-escin-permeabilized intrapulmonary bronchial Smooth Muscle of the rat induced force when the Ca2+ concentration was clamped at 1 microM. The ACh-induced Ca2+ sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivator of Rho family of proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was significantly increased in the airway hyperresponsive rats. Thus, increased airway Smooth Muscle Contractility observed in asthmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments.
Samuel Chacko - One of the best experts on this subject based on the ideXlab platform.
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increased basal phosphorylation of detrusor Smooth Muscle myosin in alloxan induced diabetic rabbit is mediated by upregulation of rho kinase β and cpi 17
American Journal of Physiology-renal Physiology, 2006Co-Authors: Shaohua Chang, Joseph A Hypolite, Michael E Disanto, Arun Changolkar, Alan J Wein, Samuel ChackoAbstract:Urinary bladder dysfunction caused by the alteration of detrusor Smooth Muscle (DSM) is one of the complications of diabetes. It is well established that Smooth Muscle Contractility is regulated by...
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obstruction induced changes in urinary bladder Smooth Muscle Contractility a role for rho kinase
American Journal of Physiology-renal Physiology, 2003Co-Authors: Wu Bing, Shaohua Chang, Joseph A Hypolite, Michael E Disanto, Alan J Wein, Stephen A Zderic, Lester Rolf, Samuel ChackoAbstract:Detrusor Smooth Muscle (DSM) undergoes hypertrophy after partial bladder outlet obstruction (PBOO) in male rabbits, as it does in men with PBOO induced by benign prostatic hyperplasia. Despite detr...
Anthony P Sampson - One of the best experts on this subject based on the ideXlab platform.
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resolvin e1 resolvin d1 and resolvin d2 inhibit constriction of rat thoracic aorta and human pulmonary artery induced by the thromboxane mimetic u46619
British Journal of Pharmacology, 2018Co-Authors: Melanie Jannaway, Christopher Torrens, Jane Warner, Anthony P SampsonAbstract:Background and purpose The ω-6 fatty acid-derived lipid mediators such as prostanoids, thromboxane and leukotrienes have well-established roles in regulating both inflammation and Smooth Muscle Contractility. Resolvins are derived from ω-3 fatty acids and have important roles in promoting the resolution of inflammation, but their activity on Smooth Muscle Contractility is unknown. We investigated whether resolvin E1 (RvE1), resolvin D1 (RvD1) and resolvin D2 (RvD2) can modulate contractions of isolated segments of rat thoracic aorta (RTA) or human pulmonary artery (HPA) induced by the α1 -adrenoceptor agonist phenylephrine or the stable thromboxane A2 mimetic U46619. Experimental approach Contractile responses in RTA and HPA were measured using wire myography. Receptor expression was investigated by immunohistochemistry. Key results Constriction of RTA segments by U46619, but not by phenylephrine, was significantly inhibited by pretreatment for 1 or 24 h with 10-100 nM RvE1, RvD1 or RvD2. The inhibitory effect of RvE1 was partially blocked by a chemerin receptor antagonist (CCX832). RvE1 at only 1-10 nM also significantly inhibited U46619-induced constriction of HPA segments, and the chemerin receptor, GPR32 and FPR2/ALX were identified in HPA Smooth Muscle. Conclusion and implications These data suggest that resolvins or their mimetics may prove useful novel therapeutics in diseases such as pulmonary arterial hypertension, which are characterized by increased thromboxane contractile activity.
Richard M Eglen - One of the best experts on this subject based on the ideXlab platform.
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muscarinic receptor subtypes modulating Smooth Muscle Contractility in the urinary bladder
Life Sciences, 1999Co-Authors: Sharath S Hegde, Richard M EglenAbstract:Abstract Normal physiological voiding as well as generation of abnormal bladder contractions in diseased states is critically dependent on acetylcholine-induced stimulation of contractile muscarinic receptors on the Smooth Muscle (detrusor) of the urinary bladder. Muscarinic receptor antagonists are efficacious in treating the symptoms of bladder hyperactivity, such as urge incontinence, although the usefulness of available drugs is limited by undesirable side-effects. Detrusor Smooth Muscle is endowed principally with M 2 and M 3 muscarinic receptors with the former predominating in number. M 3 muscarinic receptors, coupled to stimulation of phosphoinositide turnover, mediate the direct contractile effects of acetylcholine in the detrusor. Emerging evidence suggests that M 2 muscarinic receptors, via inhibition of adenylyl cyclase, cause Smooth Muscle contraction indirectly by inhibiting sympathetically (β-adrenoceptor)-mediated relaxation. In certain diseased states, M 2 receptors may also contribute to direct Smooth Muscle contraction. Other contractile mechanisms involving M 2 muscarinic receptors, such as activation of a non-specific cationic channel and inactivation of potassium channels, may also be operative in the bladder and requires further investigation. From a therapeutic standpoint, combined blockade of M 2 and M 3 muscarinic receptors would seem to be ideal since this approach would evoke complete inhibition of cholinergically-evoked Smooth Muscle contractions. However, if either the M 2 or M 3 receptor assumes a greater pathophysiological role in disease states, then selective antagonism of only one of the two receptors may be the more rational approach. The ultimate therapeutic strategy is also influenced by the extent to which pre-junctional m 1 facilitatory and M 2 inhibitory muscarinic receptors regulate acetylcholine release and also which subtypes mediate the undesirable effects of muscarinic receptor blockade such as dry mouth. Finally, the consequence of muscarinic receptor blockade in the central nervous system on the micturition reflex, an issue which is poorly studied and seldom taken into consideration, should not be ignored.
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muscarinic receptor subtypes modulating Smooth Muscle Contractility in the urinary bladder
Life Sciences, 1999Co-Authors: Sharath S Hegde, Richard M EglenAbstract:Normal physiological voiding as well as generation of abnormal bladder contractions in diseased states is critically dependent on acetylcholine-induced stimulation of contractile muscarinic receptors on the Smooth Muscle (detrusor) of the urinary bladder. Muscarinic receptor antagonists are efficacious in treating the symptoms of bladder hyperactivity, such as urge incontinence, although the usefulness of available drugs is limited by undesirable side-effects. Detrusor Smooth Muscle is endowed principally with M2 and M3 muscarinic receptors with the former predominating in number. M3 muscarinic receptors, coupled to stimulation of phosphoinositide turnover, mediate the direct contractile effects of acetylcholine in the detrusor. Emerging evidence suggests that M2 muscarinic receptors, via inhibition of adenylyl cyclase, cause Smooth Muscle contraction indirectly by inhibiting sympathetically (beta-adrenoceptor)-mediated relaxation. In certain diseased states, M2 receptors may also contribute to direct Smooth Muscle contraction. Other contractile mechanisms involving M2 muscarinic receptors, such as activation of a non-specific cationic channel and inactivation of potassium channels, may also be operative in the bladder and requires further investigation. From a therapeutic standpoint, combined blockade of M2 and M3 muscarinic receptors would seem to be ideal since this approach would evoke complete inhibition of cholinergically-evoked Smooth Muscle contractions. However, if either the M2 or M3 receptor assumes a greater pathophysiological role in disease states, then selective antagonism of only one of the two receptors may be the more rational approach. The ultimate therapeutic strategy is also influenced by the extent to which pre-junctional M1 facilitatory and M2 inhibitory muscarinic receptors regulate acetylcholine release and also which subtypes mediate the undesirable effects of muscarinic receptor blockade such as dry mouth. Finally, the consequence of muscarinic receptor blockade in the central nervous system on the micturition reflex, an issue which is poorly studied and seldom taken into consideration, should not be ignored.