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Ziyu Liu, Nam Jeong Cho
We have previously shown that muscarinic acetylcholine receptors (mAChRs) promote global protein biosynthesis in SNU-407 colon cancer cells. To gain insight into the molecular mechanisms underlying this event, we examined whether mAChRs regulate the phosphorylation of eIF4B (eukaryotic initiation factor 4B), an essential component of the translation machinery. When SNU-407 cells were treated with the cholinergic agonist carbachol, eIF4B was phosphorylated in a dose- and time-dependent manner. This carbachol effect was almost completely blocked by the muscarinic antagonist atropine, demonstrating that mAChRs specifically mediate the phosphorylation of eIF4B...
October 20, 2016: Biochemical and Biophysical Research Communications
Junji Uno, Keisuke Obara, Hiroko Suzuki, Satomi Miyatani, Daisuke Chino, Takashi Yoshio, Yoshio Tanaka
BACKGROUND/AIMS: To investigate the potential inhibitory effects of 18 clinically available antidepressants on acetylcholine (ACh)-induced contractions in guinea pig urinary bladder smooth muscle (UBSM) in order to predict whether they may induce voiding impairment. METHODS: Concentration-response curves for ACh-induced contractions in guinea pig UBSM strips were obtained in the absence or presence of selected antidepressants. When inhibitory effects indicated competitive antagonism, pA2 values against ACh were calculated and compared to plausible antidepressant blood concentrations...
October 22, 2016: Pharmacology
Jeeyeon Kim, Miesha Farahmand, Colleen Dunn, Zoe Davies, Eric Frisbee, Carlos Milla, Jeffrey J Wine
Beta-adrenergically-stimulated sweat rates determined by evaporimetry or by sweat bubble imaging are useful for measuring CFTR function because they provide a near-linear readout across almost the full range of CFTR function. They differentiate cystic fibrosis (CF) subjects from CF carriers and carriers from controls. However, evaporimetry, unlike bubble imaging, appears to be unable to detect improved levels of CFTR function in G551D subjects taking the CFTR modulator ivacaftor. Here, we quantify the sensitivity of evaporimetry and bubble imaging methods for assessing low levels of CFTR-dependent sweat rates...
2016: PloS One
Almotasembellah Aljaafareh, Jose Ruben Valle, Yu-Li Lin, Yong-Fang Kuo, Gulshan Sharma
OBJECTIVES: Long-acting bronchodilators are mainstay treatment for moderate to severe chronic obstructive pulmonary disease. A growing body of evidence indicates an increased risk of cardiovascular events upon initiation of these medications. We hypothesize that this risk is higher in patients with chronic obstructive pulmonary disease who had a preexisting cardiovascular disease regardless of receipt of any cardiovascular medication. METHODS: A retrospective cohort of patients with a diagnosis of chronic obstructive pulmonary disease based on two outpatient visits or one inpatient visit for chronic obstructive pulmonary disease (International Classification of Diseases, 9th Edition, Clinical Modification codes 491...
2016: SAGE Open Medicine
Ching-Chung Liang, Tsong-Hai Lee, Shuenn-Dhy Chang
OBJECTIVE: To demonstrate the effect of human umbilical cord blood-derived CD34(+) cells on bladder dysfunction induced by cerebral ischemia in rats. MATERIALS AND METHODS: Female rats were subjected to either 60 minute middle cerebral artery occlusion (MCAO) or a sham operation. Rats were divided into four groups: sham operation, MCAO without treatment, infusion with 1×10(6) CD34(+) cells 30 minutes before MCAO, and infusion with 1×10(6) CD34(+) cells 3 hours after MCAO...
October 2016: Taiwanese Journal of Obstetrics & Gynecology
F Sakakibara, K Takahama, M Nanri, E Sasaki
Patients with spinal cord injury (SCI) usually develop lower urinary tract dysfunctions, including detrusor overactivity which is also known to be a risk factor for upper urinary tract dysfunction. Antimuscarinic agents, such as propiverine, have been used clinically for the treatment of detrusor overactivity. Also, propiverine has been known to possess antagonistic activity against L-type Ca(2+) channels and transient receptor potential vanilloid subtype 1 (TRPV1), in addition to activity against muscarinic receptors...
September 2016: Drug Research
Tareq Abu-Izneid, Aneela Maalik, Saud Bawazeer, Ajmal Khan, Abdur Rauf, Taibi Ben Hadda, Haroon Khan, Mohamed Fawzy Ramadan, Imran Khan, Mohammad S Mubarak, Ghias Uddin, Alia Bahadar, Shujaat Ali Khan
BACKGROUND: Pistacia integerrima has many medicinal uses in therapeutic as well as folk medicine. P. integerrima has been used for the treatment of different ailments such as blood purifier, anti-inflammatory, and as remedy for gastrointestinal disorders such as vomiting and diarrhea, expectorant, cough, asthma and fever. OBJECTIVE: The main objective of this research work was to evaluate the effect of pistagremic acid (PA) isolated from the galls of Pistacia integerima in acute toxicity and gastrointestinal (GIT) motility tests...
October 7, 2016: Medicinal Chemistry
Tanja Mayer, Jürgen Kopitz, Konstanze Plaschke, Johanna Weiss, Hanna M Seidling, Walter E Haefeli
OBJECTIVE: The anticholinergic activity (AA) assay is a common method to determine a patient's anticholinergic load. Several limitations, however, are expected when applying the AA assay to patients or using drug scales to estimate anticholinergic burden based on AA levels. This study aims to demonstrate common pitfalls in an experimental setting and outline their clinical consequences. METHODS: The AA was analyzed for five drugs with reported interaction with muscarinic receptors...
August 4, 2016: American Journal of Geriatric Psychiatry
Lourdes Dias, Mariana A P Rodrigues, Bruna R Inoue, Renata L Rodrigues, André L Rennó, Valéria B de Souza, Frank D Torres-Huaco, Norma C Sousa, Alessandra Stroka, Anibal R Melgarejo, Stephen Hyslop
In this work, we examined some mechanisms involved in the hypotension caused by Lachesis muta (South American bushmaster) venom in anesthetized rats. Venom (1.5 mg/kg, i.v.) caused immediate hypotension that was maximal after 5 min and gradually returned to baseline over 60 min. Pretreatment of rats with the non-selective nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) did not attenuate the early phase of venom-induced hypotension, but abolished the recovery phase and resulted in rapid death; a similar effect was observed with the soluble guanylate cyclase (sGC) inhibitor ODQ...
October 5, 2016: Toxicon: Official Journal of the International Society on Toxinology
Zhong Jin
Covering: July 2012 to June 2015. Previous review: Nat. Prod. Rep., 2013, 30, 869-915The structurally diverse imidazole-, oxazole-, and thiazole-containing secondary metabolites are widely distributed in terrestrial and marine environments, and exhibit extensive pharmacological activities. In this review the latest progress involving the isolation, biological activities, and chemical and biogenetic synthesis studies on these natural products has been summarized.
September 16, 2016: Natural Product Reports
Sudarat Nimitvilai, Chang You, Devinder S Arora, Maureen A McElvain, Bertha J Vandegrift, Mark S Brodie, John J Woodward
Drugs of abuse increase the activity of dopaminergic neurons of the ventral tegmental area (VTA), and output from the VTA is critical for both natural and drug-induced reward and reinforcement. Ethanol and the abused inhalant toluene both enhance VTA neuronal firing, but the mechanisms of this effect is not fully known. In this study, we used extracellular recordings to compare the actions of toluene and ethanol on DA VTA neurons. Both ethanol and toluene increased the firing rate of DA neurons, although toluene was ~100 times more potent than ethanol...
2016: Frontiers in Neuroscience
Supriyo Bhattacharya, Romelia Salomon-Ferrer, Sangbae Lee, Nagarajan Vaidehi
GPCRs are transmembrane receptors involved in diverse biological functions. Despite the diversity in their amino acid sequences, class A GPCRs exhibit a conserved structural topology and possibly common mechanism of receptor activation. To understand how this high sequence diversity translates to a conserved functional mechanism, we have compared the dynamic behavior of eight class A GPCRs comprising of six biogenic amine receptors, and the adenosine A2A and a peptide receptor protease activated receptor 1...
October 6, 2016: Journal of Chemical Theory and Computation
Ila Pant, S Girish Rao, Paturu Kondaiah
Oral submucous fibrosis (OSF) is potentially premalignant with progressive and irreversible extracellular matrix deposition accompanied by epithelial atrophy and like other fibrotic disorders, is primarily a TGF-β driven disease. OSF is caused by prolonged chewing of areca nut. Our previous studies reported a pivotal role for TGF-β activation and its effects contributing to OSF. However, the mechanism for activation of TGF-β signaling in OSF is still unknown. In this study we demonstrate activation of TGF-β signaling with sub-cytotoxic dose of areca nut in epithelial cells and discovered a key role for pJNK in this process...
October 6, 2016: Scientific Reports
Yao Chou Tsai, Lori Birder, Hann-Chorng Kuo
PURPOSE: The aim of this study was to analyze patterns of sensory protein expression and urothelial dysfunction in ketamine-related cystitis (KC) in humans. METHODS: Biopsies of bladder mucosa were performed in 29 KC patients during cystoscopy. Then specimens were analyzed for tryptase, zonula occludens-1 (ZO-1), E-cadherin, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) with immunofluorescence staining and quantification. In addition, 10 healthy control bladder specimens were analyzed and compared with the KC specimens...
September 2016: International Neurourology Journal
Ofra Barchad-Avitzur, Michael F Priest, Noa Dekel, Francisco Bezanilla, Hanna Parnas, Yair Ben-Chaim
G protein-coupled receptors (GPCRs) mediate many signal transduction processes in the body. The discovery that these receptors are voltage-sensitive has changed our understanding of their behavior. The M2 muscarinic acetylcholine receptor (M2R) was found to exhibit depolarization-induced charge movement-associated currents, implying that this prototypical GPCR possesses a voltage sensor. However, the typical domain that serves as a voltage sensor in voltage-gated channels is not present in GPCRs, making the search for the voltage sensor in the latter challenging...
October 4, 2016: Biophysical Journal
Mohamed B Abou-Donia, Briana Siracuse, Natasha Gupta, Ashly Sobel Sokol
Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as "cholinergic crisis" (i...
October 5, 2016: Critical Reviews in Toxicology
Marlene A Wilson, Jim R Fadel
Cholinergic activation regulates cognitive function, particularly long-term memory consolidation. This Review presents an overview of the anatomical, neurochemical, and pharmacological evidence supporting the cholinergic regulation of Pavlovian contextual and cue-conditioned fear learning and extinction. Basal forebrain cholinergic neurons provide inputs to neocortical regions and subcortical limbic structures such as the hippocampus and amygdala. Pharmacological manipulations of muscarinic and nicotinic receptors support the role of cholinergic processes in the amygdala, hippocampus, and prefrontal cortex in modulating the learning and extinction of contexts or cues associated with threat...
October 5, 2016: Journal of Neuroscience Research
Ching Kuo Tan, Gui Quan Say, James B Geake
Tiotropium bromide is a long-acting inhaled muscarinic antagonist used in patients with chronic respiratory disease. It has been available since 2002 as a single-dose dry powder formulation via the HandiHaler(®) dry powder inhaler (DPI) device, and since 2007 as the Respimat(®) SoftMist™ Inhaler (SMI). The latter is a novel method of medication delivery that utilizes a multidose aqueous solution to deliver the drug as a fine mist. Potential benefits include more efficient drug deposition throughout the respiratory tract, reduced systemic exposure, and greater ease of use and patient satisfaction compared with the use of HandiHaler DPI...
2016: Therapeutics and Clinical Risk Management
Wei-Chia Lee, You-Lin Tain, Kay L H Wu, Steve Leu, Julie Y H Chan
Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE...
October 5, 2016: Scientific Reports
Marina Basalay, Svetlana Mastitskaya, Aleksander Mrochek, Gareth L Ackland, Ana Gutierrez Del Arroyo, Jenifer Sanchez, Per-Ove Sjoquist, John Pernow, Alexander V Gourine, Andrey Gourine
AIMS: Although the nature of the humoral factor which mediates cardioprotection established by remote ischaemic conditioning (RIc) remains unknown, parasympathetic (vagal) mechanisms appear to play a critical role. As the production and release of many gut hormones is modulated by the vagus nerve, here we tested the hypothesis that RIc cardioprotection is mediated by the actions of glucagon-like peptide-1 (GLP-1). METHODS AND RESULTS: A rat model of myocardial infarction (coronary artery occlusion followed by reperfusion) was used...
October 4, 2016: Cardiovascular Research
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