Mechanopharmacology of Rho-kinase antagonism in airway smooth muscle and potential new therapy for asthma.


:The principle of mechanopharmacology of airway smooth muscle (ASM) is based on the premise that physical agitation, such as pressure oscillation applied to an airway, is able to induce bronchodilation by reducing contractility and softening the cytoskeleton of ASM. Although the underlying mechanism is not entirely clear, there is evidence to suggest that large-amplitude stretches are able to disrupt the actomyosin interaction in the crossbridge cycle and weaken the cytoskeleton in ASM cells. Rho-kinase is known to enhance force generation and strengthen structural integrity of the cytoskeleton during smooth muscle activation and plays a key role in the maintenance of force during prolonged muscle contractions. Synergy in relaxation has been observed when the muscle is subject to oscillatory length change while Rho-kinase is pharmacologically inhibited. In this review, inhibition of Rho-kinase coupled to therapeutic pressure oscillation applied to the airways is explored as a combination treatment for asthma.


Pharmacol Res


Pharmacological research


Wang L,Chitano P,Seow CY




Has Abstract


2020-09-01 00:00:00












  • T cell toxicity of HIV latency reversing agents.

    abstract::Combination antiretroviral therapy reduces morbidity and mortality in HIV infected patients. However, the cure of HIV infection is hindered by the persistence of the latent HIV reservoir. Latency reversing agents (LRAs) are developed to target the HIV latently infected cells for HIV reactivation. In addition to revers...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Zhao M,De Crignis E,Rokx C,Verbon A,van Gelder T,Mahmoudi T,Katsikis PD,Mueller YM

    更新日期:2019-01-01 00:00:00

  • Exogenous insulin-like growth factor (IGF)-1 improves the impaired healing of gastric mucosal lesions in diabetic rats.

    abstract:BACKGROUND:We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of IGF-1 on these lesions. METHODS:Experiments were performed on rats injected with streptozotocin (STZ, 70 mg kg(-1), i.p.) 5 weeks prior to the experimental session. Diabetic ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Korolkiewicz RP,Tashima K,Fujita A,Kato S,Takeuchi K

    更新日期:2000-02-01 00:00:00

  • Effect of DL-nebivolol, its enantiomers and metabolites on the intracellular production of superoxide and nitric oxide in human endothelial cells.

    abstract::Nebivolol, a third generation selective beta(1)-adrenoceptor (beta(1)-AR) antagonist, has been reported to reduce intracellular oxidative stress and to induce the release of nitric oxide (NO) from the endothelium. Nebivolol is also subjected to a complex metabolic process where glucuronidation, aromatic and alicyclic ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Evangelista S,Garbin U,Pasini AF,Stranieri C,Boccioletti V,Cominacini L

    更新日期:2007-04-01 00:00:00

  • Lipocalin-2 and iron trafficking in the tumor microenvironment.

    abstract::Iron is an essential element for virtually all organisms. It facilitates cell proliferation and growth but also contributes to major hallmarks of cancer such as tumor initiation, growth, and metastasis. Often, iron handling of tumor cells is disturbed, with altered iron acquisition, efflux, and storage. Targeting pert...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Jung M,Mertens C,Bauer R,Rehwald C,Brüne B

    更新日期:2017-06-01 00:00:00

  • Histamine in diabetes: Is it time to reconsider?

    abstract::The first studies of histamine and diabetes date back to the 1950s. Since that time the involvement of histamine in diabetes was related to its well known vasoactive properties and permeability leakage effects. In particular, the first evidence for a correlation between histamine and diabetes arose in 1989 when an inc...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Pini A,Obara I,Battell E,Chazot PL,Rosa AC

    更新日期:2016-09-01 00:00:00

  • Isobolographic analysis of the antinociceptive interactions of clonidine with nonsteroidal anti-inflammatory drugs.

    abstract::The present study was undertaken to characterize the interactions between nonsteroidal anti-inflammatory drugs and the alpha(2)-adrenoceptor agonist clonidine in an acute nociceptive test. The writhing test was selected as a model of acute visceral pain. Isobolograms were constructed to assess the interactions of clon...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Miranda HF,Pinardi G

    更新日期:2004-09-01 00:00:00

  • Funny channels in the control of cardiac rhythm and mode of action of selective blockers.

    abstract::"Funny" (f) channels underlie the cardiac "pacemaker"I(f) current, originally described as an inward current activated on hyperpolarization to the diastolic range of voltages in sino-atrial node myocytes [Brown, HF, DiFrancesco, D, Noble, SJ. How does adrenaline accelerate the heart? Nature 1979;280:235-236]. The invo...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: DiFrancesco D

    更新日期:2006-05-01 00:00:00

  • Piezo2 channel in nodose ganglia neurons is essential in controlling hypertension in a pathway regulated directly by Nedd4-2.

    abstract::Baroreflex plays a crucial role in regulation of arterial blood pressure (BP). Recently, Piezo1 and Piezo2, the mechanically-activated (MA) ion channels, have been identified as baroreceptors. However, the underlying molecular mechanism for regulating these baroreceptors in hypertension remains unknown. In this study,...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Huo L,Gao Y,Zhang D,Wang S,Han Y,Men H,Yang Z,Qin X,Wang R,Kong D,Bai H,Zhang H,Zhang W,Jia Z

    更新日期:2020-12-19 00:00:00

  • Identification of an IKKβ inhibitor for inhibition of inflammation in vivo and in vitro.

    abstract::Targeting on the IKKβ to discover anti-inflammatory drugs has been launched for ten years, due to its predominant role in canonical NF-κB signaling. In the current study, we identified a novel IKKβ inhibitor, ellipticine (ELL), an alkaloid isolated from Ochrosia elliptica and Rauvolfia sandwicensis. We found that ELL ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Chen Q,Liu J,Zhuang Y,Bai LP,Yuan Q,Zheng S,Liao K,Khan MA,Wu Q,Luo C,Liu L,Wang H,Li T

    更新日期:2019-11-01 00:00:00

  • Bombycis corpus extract prevents amyloid-beta-induced cytotoxicity and protects superoxide dismutase activity in cultured rat astrocytes.

    abstract::Bombycis corpus(BC) or Bombyx Batryticatus, a batryticated silkworm and white-stiff silkworm, is a drug consisting of the dried larva of silkworm, Mobyz mori L., dead and stiffened due to the infection of Beauveria (Bals.) Vuill. In the present study, we have examined the protective effect of the water extracts agains...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Kim HJ,Lee WH,Yoon CH,Jeong JC,Nam KS,Kim HM,Choo YK,Lee MC,Kim CH

    更新日期:2001-01-01 00:00:00

  • The therapeutic role of long non-coding RNAs in human diseases: A focus on the recent insights into autophagy.

    abstract::Long non-coding RNA (lncRNA) is a class of non-coding RNA with ≥200 nucleotides in length which are involved as critical regulators in various cellular processes. LncRNAs contribute to the development and progression of many human diseases. Autophagy is a key catabolic process which helps to maintain the cellular home...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Barangi S,Hayes AW,Reiter R,Karimi G

    更新日期:2019-04-01 00:00:00

  • Sesterterpene MHO7 suppresses breast cancer cells as a novel estrogen receptor degrader.

    abstract::Breast cancer, the most prevalent cancer in women, remains the second in the list of cancer mortality, the majority of these fatalities resulted from estrogen receptor alpha (ERα) positive disease. ERα is well known for its function on breast cancer initiation and development and has become the most successful biomark...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Zhao Y,Zhao C,Lu J,Wu J,Li C,Hu Z,Tian W,Yang L,Xiang J,Zhou H,Deng Z,Huang J,Hong K

    更新日期:2019-08-01 00:00:00

  • Alzheimer's disease: Key developments support promising perspectives for therapy.

    abstract::Alzheimer's is the neurodegenerative disease affecting the largest number of patients in the world. In spite of the intense research of the last decades, progress about its knowledge and therapy was limited. In particular, various cytotoxic processes remained debated, while the few drugs approved for therapy were of o...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Meldolesi J

    更新日期:2019-08-01 00:00:00

  • Targeting SHP2 as a promising strategy for cancer immunotherapy.

    abstract::Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) is a major phosphatase involved in several cellular processes. In recent years, SHP2 has been the focus of significant attention in human diseases, particular in cancer. Several studies have shown that SHP2 plays an important role in regulating immune cel...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Liu Q,Qu J,Zhao M,Xu Q,Sun Y

    更新日期:2020-02-01 00:00:00

  • Differential in vivo and in vitro effect of gentamicin on glutamate synthesis and glutamate deamination in rabbit kidney-cortex tubules and mitochondria.

    abstract::The effect of gentamicin on both glutamate synthesis and glutamate deamination was studied in kidney-cortex mitochondria and tubules isolated from both control and gentamicin-treated animals. In kidney-cortex mitochondria which were permeabilized in order to make a free access of substrates and antibiotic to the gluta...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Bryła J,Lietz T,Jarzyna R,Michalik M,Pietkiewicz J

    更新日期:1992-12-01 00:00:00

  • Carnosol-mediated Sirtuin 1 activation inhibits Enhancer of Zeste Homolog 2 to attenuate liver fibrosis.

    abstract::Quiescent hepatic stellate cell (HSC) activation and subsequent conversion into myofibroblasts is the central event in hepatic fibrosis pathogenesis. Epithelial-mesenchymal transition (EMT), another vital participant in liver fibrosis, has the potential to initiate HSC activation, which promotes abundant myofibroblast...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Zhao H,Wang Z,Tang F,Zhao Y,Feng D,Li Y,Hu Y,Wang C,Zhou J,Tian X,Yao J

    更新日期:2018-02-01 00:00:00

  • Evidence for oxidative stress in the hepatic mitochondria of bile duct ligated rats.

    abstract::Lipid peroxidation increased both in the liver homogenates and in the hepatic mitochondrial fraction of bile duct ligated (BDL)-rats. Although mitochondrial superoxide dismutase (SOD) activity did not change in the liver, glutathione (GSH) levels and glutathione peroxidase (GSH-Px) activity decreased in hepatic mitoch...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Alptekin N,Mehmetçik G,Uysal M,Aykaç-toker G

    更新日期:1997-09-01 00:00:00

  • PI3K signal and DNA repair: a short commentary.

    abstract::PI3K was originally discovered as a lipid kinase involved in the phosphorylation of the inositol ring in position -3, leading to the synthesis of phosphatidyl-inositol-3-4 bisphosphate. The enzyme purified from rat liver is an heterodimer of two subunits of 85 and 110 KD respectively: it phosphorylates the D3 hydroxyl...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Chiarugi V

    更新日期:1997-04-01 00:00:00

  • Tumor-derived extracellular vesicles: Regulators of tumor microenvironment and the enlightenment in tumor therapy.

    abstract::In recent decades, extracellular vesicles (EVs) have been proven to establish an important bridge of communication between cells or cells and their microenvironment. It is well known that EVs play crucial roles in many human diseases, especially in tumors. Tumor-derived EVs (TEVs) are not only involved in epithelial-m...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Chen J,Fei X,Wang J,Cai Z

    更新日期:2020-09-01 00:00:00

  • Targeting nanoparticles to cancer.

    abstract::Nanotechnology applications in medicine, termed as nanomedicine, have introduced a number of nanoparticles of variable chemistry and architecture for cancer imaging and treatment. Nanotechnology involves engineering multifunctional devices with dimensions at the nanoscale, similar dimensions as those of large biologic...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Wang M,Thanou M

    更新日期:2010-08-01 00:00:00

  • Dopaminergic projection to the septum mediates facilitatory effect of angiotensins on recognition memory in rats.

    abstract::We have previously reported that the dopaminergic projection from A10 ventral tegmental neurons to the central amygdala is, in part, responsible for the facilitatory effect of angiotensin II (AII) and its 3-7 fragment [AII(3-7)] on the retrieval of information in memory motivated affectively and also on recognition me...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Winnicka MM,Braszko JJ,Wiśniewski K

    更新日期:1997-11-01 00:00:00

  • The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis.

    abstract::Short-chain fatty acids (SCFAs), mainly including acetate, propionate, and butyrate, are metabolites produced during the bacterial fermentation of dietary fiber in the intestinal tract. They are believed to be essential factors affecting host health. Most in vitro and ex vivo studies have shown that SCFAs affect the r...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Liu P,Wang Y,Yang G,Zhang Q,Meng L,Xin Y,Jiang X

    更新日期:2021-01-09 00:00:00

  • Novel celecoxib analogues inhibit glial production of prostaglandin E2, nitric oxide, and oxygen radicals reverting the neuroinflammatory responses induced by misfolded prion protein fragment 90-231 or lipopolysaccharide.

    abstract::We tested the efficacy of novel cyclooxygenase 2 (COX-2) inhibitors in counteracting glia-driven neuroinflammation induced by the amyloidogenic prion protein fragment PrP90-231 or lipopolysaccharide (LPS). In search for molecules with higher efficacy than celecoxib, we focused our study on its 2,3-diaryl-1,3-thiazolid...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Villa V,Thellung S,Bajetto A,Gatta E,Robello M,Novelli F,Tasso B,Tonelli M,Florio T

    更新日期:2016-11-01 00:00:00

  • The influence of simvastatin on lipase and cholesterol esterase activity in the serum of men with coronary heart disease.

    abstract::Several studies have demonstrated that any beneficial effects of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), of which simvastatin (Merck Sharp & Dohme) is an example, on coronary events are linked to their hypocholesterolemic properties. The in vivo effects of simvastatin treatment ...

    journal_title:Pharmacological research

    pub_type: 临床试验,杂志文章


    authors: Pioruńska-Stolzmann M,Pioruńska-Mikołajczak A

    更新日期:2001-04-01 00:00:00

  • MicroRNAs in chronic airway diseases: Clinical correlation and translational applications.

    abstract::MicroRNAs (miRNAs) are short single-stranded RNAs that have pivotal roles in disease pathophysiology through transcriptional and translational modulation of important genes. It has been implicated in the development of many diseases, such as stroke, cardiovascular conditions, cancers and inflammatory airway diseases. ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Tan BWQ,Sim WL,Cheong JK,Kuan WS,Tran T,Lim HF

    更新日期:2020-10-01 00:00:00

  • Biosimilars in rheumatology.

    abstract::Biotechnologicals are an invaluable resource in the treatment of patients with inflammatory rheumatic diseases (IRD) non-responsive or intolerant to conventional therapies. However, they are the main driver for increase in direct costs and represent a significant economic burden to healthcare systems worldwide. Since ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Araújo FC,Gonçalves J,Fonseca JE

    更新日期:2019-11-01 00:00:00

  • Hypolipidaemic activity in rodents of boron analogs of phosphonoacetates and cyanoborane adducts of dialkyl aminomethylphosphonates.

    abstract::Boron analogues of phosphonoacetates proved to be potent hypolipidaemic agents in rodents, lowering both serum cholesterol and triglyceride levels. (C2H5O)3PBH2COOCH3 proved to be the most effective agent in mice, lowering serum cholesterol 46% and serum triglycerides 54% after 16 days. (C2H5O)3PBH2COOH and Na+H+(C2H5...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Hall IH,Wong OT,Sood A,Sood CK,Spielvogel BF,Shrewsbury RP,Morse KW

    更新日期:1992-04-01 00:00:00

  • Implication of STARD5 and cholesterol homeostasis disturbance in the endoplasmic reticulum stress-related response induced by pro-apoptotic aminosteroid RM-133.

    abstract::The aminosteroid derivative RM-133 is an effective anticancer molecule for which proof of concept has been achieved in several mouse xenograph models (HL-60, MCF-7, PANC-1 and OVCAR-3). To promote this new family of molecules toward a clinical phase 1 trial, the mechanism of action governing the anticancer properties ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Perreault M,Maltais R,Kenmogne LC,Létourneau D,LeHoux JG,Gobeil S,Poirier D

    更新日期:2018-02-01 00:00:00

  • Gastroprotective and anti-inflammatory effects of resin from Protium heptaphyllum in mice and rats.

    abstract::The natural resin collected from the trunk wood of Protium heptaphyllum is used in folk medicine to treat inflammatory conditions and to hasten wound repair. In the search of new potential anti-inflammatory agents with gastroprotective property, the present study evaluated its effects in experimental models of gastric...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Oliveira FA,Vieira-Júnior GM,Chaves MH,Almeida FR,Florêncio MG,Lima RC Jr,Silva RM,Santos FA,Rao VS

    更新日期:2004-02-01 00:00:00

  • Carbon nanomaterials and amyloid-beta interactions: potentials for the detection and treatment of Alzheimer's disease?

    abstract::Carbon-based nanomaterials have unique physicochemical properties relevant to the diagnosis and treatment of various diseases. There have been many reports indicating that carbon nanomaterials (CNMs) can interact and perturb biomolecules such as proteins and amyloid structures. This review is an attempt to reflect the...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Mohajeri M,Behnam B,Barreto GE,Sahebkar A

    更新日期:2019-05-01 00:00:00