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Author (up) Alvarez, J.; Fadic, R. file  url
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  Title Assembly and disassembly of axonal microtubules of the toad Xenopus laevis under the effect of temperature Type Journal Article
  Year 1992 Publication The Journal of Experimental Zoology Abbreviated Journal J Exp Zool  
  Volume 264 Issue 3 Pages 261-266  
  Keywords Animals; Axons/*physiology; Cytoplasm/metabolism; Kinetics; Microtubules/*physiology; Seasons; *Temperature; Tubulin/metabolism; Xenopus laevis  
  Abstract In toads Xenopus laevis living at 11 degrees (winter), the microtubular density of 4-microns myelinated axons of lumbosacral nerves was assessed with the electron microscope. In controls, the density was 11.2 microtubules/microns2. In nerves incubated at 0 degrees, microtubules decreased following a simple exponential curve with a half time of 4.7 min (k = 0.149 min-1); residual microtubules were 4.5%. After rewarming, the full complement of microtubules reappeared within 60 min. In steady state, the microtubular density exhibited a linear relationship with temperature (range: 0-22 degrees; slope 0.94 microtubules/microns 2 per degree; r, 0.96). After heating the nerve by 11 degrees above the physiological temperature, microtubules increased by 83%, whereby the pool of unpolymerized tubulin was at least 2.7 mg/ml of axoplasm. A seasonal variation of the microtubular density was observed which accorded with the environmental temperature. The macroscopic kinetics of microtubule disassembly in the axoplasm is similar to that reported for purified tubulin but that of assembly is slower. Microtubules of peripheral axons of Xenopus are cold-labile and vary during the annual cycle.  
  Call Number Serial 1174  
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Author (up) Amici, M.; Eusebi, F.; Miledi, R. file  url
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  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  
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Author (up) Berzins, D.W.; Bundy, K.J. file  url
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  Title Bioaccumulation of lead in Xenopus laevis tadpoles from water and sediment Type Journal Article
  Year 2002 Publication Environment International Abbreviated Journal Environ Int  
  Volume 28 Issue 1-2 Pages 69-77  
  Keywords Animals; Body Weight/drug effects; Environmental Pollutants/*pharmacokinetics/toxicity; Fresh Water/chemistry; Geologic Sediments/chemistry; Larva/*chemistry/growth & development; Lead/*pharmacokinetics/toxicity; Louisiana; *Xenopus  
  Abstract The overall objective of this research was to monitor the uptake kinetics of lead in an amphibian model and correlate metal content with embryo development. Based upon the concentration of lead found in the water and sediment of a Louisiana swamp adjacent to a Superfund site, a controlled laboratory experiment exploring lead uptake from water and sediment by Xenopus laevis tadpoles was conducted. For 5 weeks, tadpoles were exposed to water and a simulated sediment, kaolin, spiked with 1, 5, or 10 times the concentration of lead found in field water and sediment samples. Additionally, organisms were exposed to the 5 x condition for 3 and 6 weeks. The experimental controls consisted of unexposed tadpoles and ones exposed to lead originating from water or sediment exclusively. At the end of the exposure periods, developmental data, i.e., body weight and developmental stage, were recorded, and the tadpoles were analyzed for whole body lead concentration. Lead extraction was accomplished by dry ashing, and its amount was quantified polarographically. Results showed that lead inhibited the normal development of these amphibians, in a manner that generally was more severe as exposure level increased. The hindrance of tadpole development also coincided with an increase in whole body lead concentration at higher exposures. Temporally, at the 5 x exposure concentration, the mean lead level increased with time, but this difference was not statistically significant (P<.05). Additionally, control animals exposed to lead (either in water or in sediment) showed no statistical difference with regard to weight and lead uptake, indicating that lead originating from both water and sediment is incorporated into the tadpole. The controlled laboratory experimental protocol used here is thus capable of investigating the uptake of a single metal (Pb in this case) and determining its effect on the development of tadpoles while differentiating the significance of multiple sources of exposure.  
  Call Number Serial 1183  
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Author (up) Briggs, C.A.; Gronlien, J.H.; Curzon, P.; Timmermann, D.B.; Ween, H.; Thorin-Hagene, K.; Kerr, P.; Anderson, D.J.; Malysz, J.; Dyhring, T.; Olsen, G.M.; Peters, D.; Bunnelle, W.H.; Gopalakrishnan, M. file  url
openurl 
  Title Role of channel activation in cognitive enhancement mediated by alpha7 nicotinic acetylcholine receptors Type Journal Article
  Year 2009 Publication British Journal of Pharmacology Abbreviated Journal Br J Pharmacol  
  Volume 158 Issue 6 Pages 1486-1494  
  Keywords Allosteric Regulation; Animals; Avoidance Learning/drug effects; Azabicyclo Compounds/administration & dosage/*pharmacology; Behavior, Animal/drug effects; Cell Line; Cognition Disorders/drug therapy/physiopathology; Dose-Response Relationship, Drug; Furans/administration & dosage/*pharmacology; Humans; Male; Mice; Nicotinic Agonists/*pharmacology; Oocytes/drug effects/metabolism; Oxadiazoles/administration & dosage/*pharmacology; Pyridazines/pharmacology; Pyrroles/pharmacology; Rats; Receptors, Nicotinic/*drug effects/metabolism; Xenopus laevis; alpha7 Nicotinic Acetylcholine Receptor  
  Abstract BACKGROUND AND PURPOSE: Several agonists of the alpha7 nicotinic acetylcholine receptor (nAChR) have been developed for treatment of cognitive deficits. However, agonist efficacy in vivo is difficult to reconcile with rapid alpha7 nAChR desensitization in vitro; and furthermore, the correlation between in vitro receptor efficacy and in vivo behavioural efficacy is not well delineated. The possibility that agonists of this receptor actually function in vivo as inhibitors via desensitization has not been finally resolved. EXPERIMENTAL APPROACH: Two structurally related alpha7 nAChR agonists were characterized and used to assess the degree of efficacy required in a behavioural paradigm. KEY RESULTS: NS6784 activated human and rat alpha7 nAChR with EC(50)s of 0.72 and 0.88 microM, and apparent efficacies of 77 and 97% respectively. NS6740, in contrast, displayed little efficacy at alpha7 nAChR (<2% in oocytes, < or =8% in GH4C1 cells), although its agonist-like properties were revealed by adding a positive allosteric modulator of alpha7 nAChRs or using the slowly desensitizing alpha7V274T receptor. In mouse inhibitory avoidance (IA) memory retention, NS6784 enhanced performance as did the 60% partial agonist A-582941. In contrast, NS6740 did not enhance performance, but blocked effects of A-582941. CONCLUSIONS AND IMPLICATIONS: Collectively, these findings suggest that a degree of alpha7 nAChR agonist efficacy is required for behavioural effects in the IA paradigm, and that such behavioural efficacy is not due to alpha7 nAChR desensitization. Also, a partial agonist of very low efficacy for this receptor could be used as an inhibitor, in the absence of alpha7 nAChR antagonists with favourable CNS penetration.  
  Call Number Serial 1881  
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Author (up) Bucher, D.; Buchner, E. file  url
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  Title Stimulating PACalpha increases miniature excitatory junction potential frequency at the Drosophila neuromuscular junction Type Journal Article
  Year 2009 Publication Journal of Neurogenetics Abbreviated Journal J Neurogenet  
  Volume 23 Issue 1-2 Pages 220-224  
  Keywords Adenylyl Cyclases/*physiology; Animals; Cyclic AMP/physiology; Drosophila/*physiology; Enzyme Activation/radiation effects; Excitatory Postsynaptic Potentials/physiology; Light Signal Transduction/physiology; Miniature Postsynaptic Potentials/physiology; Motor Neurons/enzymology; Neuromuscular Junction/*physiology; Photic Stimulation/methods; Synapses/enzymology/physiology  
  Abstract Photoactivated adenylate cyclase alpha (PACalpha) is a light-activated adenylate cyclase that was originally cloned from the eye spot of the protozoan Euglena gracilis. PACalpha has been shown to rapidly increase intracellular cyclic adenosine monophosphate (cAMP) in vivo in Xenopus oocytes and HEK293 cells, increase the spike width in Aplysia sensory neurons, and modify behavior in Drosophila. Using the GAL4 UAS system, we heterologously expressed PACalpha in motorneurons and quantified the effects of its activation at the neuromuscular junction of the Drosophila third instar wandering larva, a well-characterized model synapse. By recording from body-wall muscle 6, we show that the presynaptic activation of PACalpha with blue light significantly increased miniature excitatory junction potential (mEJP) frequency in the presence of calcium with a delay of about 1 minute. Similar effects have been observed in previous studies that utilized adenylate cyclase agonists (Forskolin) or membrane-permeable cAMP analogs [dibutyryl cAMP and 4-chlorophenylthio-(CPT)-cAMP] to increase presynaptic cAMP concentrations. PACalpha's efficacy in combination with its specificity make it an invaluable tool for the rapid regulation of cAMP in vivo and for investigating the mechanisms by which cAMP can modulate synaptic transmission and neuronal plasticity in Drosophila.  
  Call Number Serial 1255  
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