more information
Search within Results:

Select All    Deselect All
 |   | 
Details
   print
  Records Links
Author (up) Amici, M.; Eusebi, F.; Miledi, R. file  url
openurl 
  Title Effects of the antibiotic gentamicin on nicotinic acetylcholine receptors Type Journal Article
  Year 2005 Publication Neuropharmacology Abbreviated Journal Neuropharmacology  
  Volume 49 Issue 5 Pages 627-637  
  Keywords Animals; Anti-Bacterial Agents--pharmacology; Cochlea--drug effects; DNA, Complementary--biosynthesis; Electrophysiology; Gentamicins--pharmacology; Humans; Membrane Potentials--drug effects, physiology; Mice; Nicotinic Antagonists; Oocytes--metabolism; Patch-Clamp Techniques; RNA, Complementary--biosynthesis; Receptors, Nicotinic--biosynthesis, drug effects, genetics; Torpedo; Vestibule, Labyrinth--drug effects; Xenopus; alpha7 Nicotinic Acetylcholine Receptor  
  Abstract Medical treatment with the aminoglycosidic antibiotic gentamicin may produce side effects that include neuromuscular blockage and ototoxicity; which are believed to result from a dysfunction of nicotinic acetylcholine receptors (AChRs). Gentamicin is known to reversibly block ACh-currents generated by the activation of muscle-type alphabetagammadelta-AChR and neuronal alpha9-AChR. We studied the effects of gentamicin on heteromeric alphabetagammadelta-AChR and homomeric alpha7-AChR expressed in Xenopus oocytes. Prolonged treatment with gentamicin, and other antibiotics, differentially altered alphabetagammadelta- and alpha7-AChR responses. Specifically, gentamicin accelerated desensitization and did not reduce ACh-currents in oocytes expressing alphabetagammadelta-AChRs, whereas ACh-currents were reduced and desensitization was unaltered in oocytes expressing alpha7-AChRs. Moreover, acutely applied gentamicin acted as a competitive antagonist on both types of receptors and increased the rate of desensitization in alphabetagammadelta-AChR while reducing the rate of desensitization in alpha7-AChR. This data helps to better understand the action of gentamicin on muscle and nervous tissues, providing mechanistic insights that could eventually lead to improving the medical use of aminoglycosides.  
  Call Number Serial 445  
Permanent link to this record
 

 
Author (up) Arias, H.R. file  url
openurl 
  Title Positive and negative modulation of nicotinic receptors Type Journal Article
  Year 2010 Publication Advances in Protein Chemistry and Structural Biology Abbreviated Journal Adv Protein Chem Struct Biol  
  Volume 80 Issue Pages 153-203  
  Keywords Acetylcholine/chemistry/physiology; Allosteric Regulation; Allosteric Site/genetics; Animals; Cholinergic Antagonists/*pharmacology/therapeutic use; Crystallography, X-Ray; Humans; Ion Channel Gating/drug effects; Mice; Nicotinic Agonists/*pharmacology/therapeutic use; Protein Structure, Tertiary; Receptors, Nicotinic/*chemistry/*physiology; Structure-Activity Relationship  
  Abstract Nicotinic acetylcholine receptors (AChRs) are one of the best characterized ion channels from the Cys-loop receptor superfamily. The study of acetylcholine binding proteins and prokaryotic ion channels from different species has been paramount for the understanding of the structure-function relationship of the Cys-loop receptor superfamily. AChR function can be modulated by different ligand types. The neurotransmitter ACh and other agonists trigger conformational changes in the receptor, finally opening the intrinsic cation channel. The so-called gating process couples ligand binding, located at the extracellular portion, to the opening of the ion channel, located at the transmembrane region. After agonist activation, in the prolonged presence of agonists, the AChR becomes desensitized. Competitive antagonists overlap the agonist-binding sites inhibiting the pharmacological action of agonists. Positive allosteric modulators (PAMs) do not bind to the orthostetic binding sites but allosterically enhance the activity elicited by agonists by increasing the gating process (type I) and/or by decreasing desensitization (type II). Instead, negative allosteric modulators (NAMs) produce the opposite effects. Interestingly, this negative effect is similar to that found for another class of allosteric drugs, that is, noncompetitive antagonists (NCAs). However, the main difference between both categories of drugs is based on their distinct binding site locations. Although both NAMs and NCAs do not bind to the agonist sites, NACs bind to sites located in the ion channel, whereas NAMs bind to nonluminal sites. However, this classification is less clear for NAMs interacting at the extracellular-transmembrane interface where the ion channel mouth might be involved. Interestingly, PAMs and NAMs might be developed as potential medications for the treatment of several diseases involving AChRs, including dementia-, skin-, and immunological-related diseases, drug addiction, and cancer. More exciting is the potential combination of specific agonists with specific PAMs. However, we are still in the beginning of understanding how these compounds act and how these drugs can be used therapeutically.  
  Call Number Serial 1886  
Permanent link to this record
 

 
Author (up) Backberg, M.; Meister, B. file  url
openurl 
  Title Abnormal cholinergic and GABAergic vascular innervation in the hypothalamic arcuate nucleus of obese tub/tub mice Type Journal Article
  Year 2004 Publication Synapse (New York, N.Y.) Abbreviated Journal Synapse  
  Volume 52 Issue 4 Pages 245-257  
  Keywords Acetylcholine/*metabolism; Adaptor Proteins, Signal Transducing; Animals; Arcuate Nucleus of Hypothalamus/blood supply/*metabolism; Blood Vessels/innervation; Carrier Proteins/metabolism; Glutamate Decarboxylase/metabolism; Immunohistochemistry; *Membrane Transport Proteins; Mice; Mutation; Obesity/*physiopathology; Polymerase Chain Reaction; Presynaptic Terminals/metabolism; Proteins/*genetics; Synaptophysin/metabolism; Vesicular Acetylcholine Transport Proteins; *Vesicular Transport Proteins; gamma-Aminobutyric Acid/*metabolism  
  Abstract Tubby and tubby-like proteins (TULPs) are encoded by members of a small gene family. An autosomal recessive mutation in the mouse tub gene leads to blindness, deafness, and maturity-onset obesity. The mechanisms by which the mutation causes the obesity syndrome has not been established. We compared obese tub/tub mice and their lean littermates in order to find abnormalities within the mediobasal hypothalamus, a region intimately associated with the regulation of body weight. Using an antiserum to the vesicular acetylcholine transporter (VAChT), a marker for cholinergic neurons, many unusually large VAChT-immunoreactive (-ir) nerve terminals, identified by colocalization with the synaptic vesicle protein synaptophysin, were demonstrated in the hypothalamic arcuate nucleus of obese tub/tub mice. Double-labeling showed that VAChT-ir nerve endings also contained glutamic acid decarboxylase (GAD), a marker for gamma-aminobutyric acid (GABA) neurons. The VAChT- and GAD-ir nerve terminals were in close contact with blood vessels, identified with antisera to platelet endothelial cell adhesion molecule-1 (PECAM; also called CD31), laminin, smooth muscle actin (SMA), and glucose transporter-1 (GLUT1). Such large cholinergic and GABAergic nerve terminals surrounding blood vessels were not seen in the arcuate nucleus of lean tub/+ mice. The presence of abnormal cholinergic/GABAergic vascular innervation in the arcuate nucleus suggests that alterations in this region, which contains neurons that receive information from the periphery and which relays information about the energy status to other parts of the brain, may be central in the development of the obese phenotype in animals with an autosomal recessive mutation in the tub gene.  
  Call Number Serial 1460  
Permanent link to this record
 

 
Author (up) Bassett, C.M.C.; Rodriguez-Leyva, D.; Pierce, G.N. file  url
openurl 
  Title Experimental and clinical research findings on the cardiovascular benefits of consuming flaxseed Type Journal Article
  Year 2009 Publication Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquee, Nutrition et Metabolisme Abbreviated Journal Appl Physiol Nutr Metab  
  Volume 34 Issue 5 Pages 965-974  
  Keywords Animals; Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; *Cardiovascular Diseases; *Dietary Supplements; *Flax; Humans; Hypertension; Hypolipidemic Agents; Lipids/blood; Mice  
  Abstract Functional foods and nutraceuticals are becoming popular alternatives to pharmacological treatments by providing health benefits and (or) reducing the risk of chronic diseases. Flaxseed is a rich source of 3 components with demonstrated cardioprotective effects: the omega-3 fatty acid alpha-linolenic acid (ALA), dietary fibre, and phytoestrogen lignans. Multiple clinical dietary intervention trials report that consuming flaxseed daily can modestly reduce circulating total cholesterol (TC) by 6%-11% and low-density lipoprotein (LDL) cholesterol by 9%-18% in normolipemic humans and by 5%-17% for TC and 4%-10% for LDL cholesterol in hypercholesterolemic patients, as well as lower various markers associated with atherosclerotic cardiovascular disease in humans. Evidence to date suggests that the dietary fibre and (or) lignan content of flaxseed provides the hypocholesterolemic action. The omega-3 ALA found in the flaxseed oil fraction also contributes to the antiatherogenic effects of flaxseed via anti-inflammatory and antiproliferative mechanisms. Dietary flaxseed may also protect against ischemic heart disease by improving vascular relaxation responses and by inhibiting the incidence of ventricular fibrillation.  
  Call Number Serial 1758  
Permanent link to this record
 

 
Author (up) Bercik, P. file  url
openurl 
  Title The microbiota-gut-brain axis: learning from intestinal bacteria? Type Journal Article
  Year 2011 Publication Gut Abbreviated Journal Gut  
  Volume 60 Issue 3 Pages 288-289  
  Keywords Animals; Bacterial Infections/*psychology; Cognition Disorders/*microbiology; Humans; Intestinal Diseases/microbiology/*psychology; Intestines/*microbiology; Mice; Symbiosis; Microbiome  
  Abstract The intestinal microbiota is a diverse and dynamic ecosystem,1 which has developed a mutualistic relationship with its host and plays a crucial role in the development of the host's innate and adaptive immune responses.2 This ecosystem serves the host by protecting against pathogens, harvesting otherwise inaccessible nutrients, aiding in neutralisation of drugs and carcinogens, and affecting the metabolism of lipids.3 Gut bacteria modulate intestinal motility, barrier function and visceral perception.4

An interaction between the intestinal microbiota and the central nervous system (CNS) may seem difficult to conceive at first sight, but clinicians are well aware of the benefit of oral antibiotics and laxatives in the treatment of hepatic encephalopathy.5 Data accumulated from animal studies indicate that there is central sensing of gastrointestinal infections. For example, acute infection with Campylobacter jejuni results in anxiety-like behaviour and rapid activation of vagal pathways prior to onset of immune responses,6 while chronic Helicobacter pylori infection in mice leads to abnormal feeding behaviour and upregulation of tumour necrosis factor α (TNFα) in the median eminence of the hypothalamus.7 Rapid and sustained gut�brain communication may confer a significant advantage to the host, as central activation in response to changes in commensals or pathogens would allow better control of gut function and immunity.
 
  Call Number Serial 2096  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print

Save Citations: