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Author (up) Alvarez, J.; Fadic, R. file  url
  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) 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
  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) Elinson, R.P. file  url
  Title Microtubules and specification of the dorsoventral axis in frog embryos Type Journal Article
  Year 1989 Publication BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology Abbreviated Journal Bioessays  
  Volume 11 Issue 5 Pages 124-127  
  Keywords Animals; Blastocyst/physiology; Cell Differentiation/*physiology; Embryonic Induction/*physiology; Female; Male; Microtubules/*physiology; Notochord/embryology; Sperm-Ovum Interactions/physiology; Xenopus laevis/*embryology  
  Abstract The body plan of the frog is set-up by a rearrangement of the egg cytoplasm shortly after fertilization. Microtubules play several roles in this critical developmental event.  
  Call Number Serial 1173  
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Author (up) Elinson, R.P.; Rowning, B. file  url
  Title A transient array of parallel microtubules in frog eggs: potential tracks for a cytoplasmic rotation that specifies the dorso-ventral axis Type Journal Article
  Year 1988 Publication Developmental Biology Abbreviated Journal Dev Biol  
  Volume 128 Issue 1 Pages 185-197  
  Keywords Animals; Benzimidazoles/pharmacology; Cell Membrane/ultrastructure; Colchicine/pharmacology; Cytoplasm/*ultrastructure; Female; Fluorescent Antibody Technique; Histocytochemistry; Immunoenzyme Techniques; Microscopy, Electron; Microtubules/drug effects/radiation effects/*ultrastructure; Nocodazole; Ovum/radiation effects/*ultrastructure; Rana pipiens; Ultraviolet Rays; Xenopus laevis  
  Abstract The dorsoventral axis of the frog embryo is specified by a rotation of the egg cytoplasm relative to the cortex. When eggs undergoing the cortical/cytoplasmic rotation were examined by immunocytochemistry and electron microscopy, an extensive array of parallel microtubules was found covering the vegetal hemisphere of the egg. The microtubules were 1-3 microns deep from the plasma membrane and were aligned parallel to the direction of rotation. They formed at the start of rotation and disappeared at its completion. Colchicine and uv irradiation, inhibitors of the rotation, prevented the formation of the parallel microtubules. Based on these properties, we suggest that the parallel microtubules serve as tracks for the cortical/cytoplasmic rotation which specifies the dorsoventral axis of the embryo.  
  Call Number Serial 1176  
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Author (up) Hall, A.C.; Griffith, T.N.; Tsikolia, M.; Kotey, F.O.; Gill, N.; Humbert, D.J.; Watt, E.E.; Yermolina, Y.A.; Goel, S.; El-Ghendy, B.; Hall, C.D. file  url
doi  openurl
  Title Cyclohexanol analogues are positive modulators of GABA(A) receptor currents and act as general anaesthetics in vivo Type Journal Article
  Year 2011 Publication European Journal of Pharmacology Abbreviated Journal Eur J Pharmacol  
  Volume 667 Issue 1-3 Pages 175-181  
  Keywords Anesthetics, General/*pharmacology; Animals; Cyclohexanols/*chemistry/*pharmacology; *Electric Conductivity; Electrophysiological Processes/drug effects; Humans; Larva/drug effects/metabolism/physiology; Oocytes/metabolism; Receptors, GABA-A/genetics/*metabolism; Xenopus laevis/genetics  
  Abstract GABA(A) receptors meet all the pharmacological criteria required to be considered important general anaesthetic targets. In the following study, the modulatory effects of various commercially available and novel cyclohexanols were investigated on recombinant human gamma-aminobutyric acid (GABA(A), alpha(1)beta(2)gamma(2s)) receptors expressed in Xenopus oocytes, and compared to the modulatory effects on GABA currents observed with exposures to the intravenous anaesthetic agent, propofol. Submaximal EC(20) GABA currents were typically enhanced by co-applications of 3-300 muM cyclohexanols. For instance, at 30 muM 2,6-diisopropylcyclohexanol (a novel compound) GABA responses were increased ~3-fold (although similar enhancements were achieved at 3 muM propofol). As regards rank order for modulation by the cyclohexanol analogues at 30 muM, the % enhancements for 2,6-dimethylcyclohexanol~2,6-diethylcyclohexanol~2,6-diisopropylcyclohexanol~2,6- di-sec-butylcyclohexanol >>2,6-di-tert-butylcyclohexanol~4-tert-butylcyclohexanol>cyclohexanol~cyclopentan ol~2-methylcyclohexanol. We further tested the potencies of the cyclohexanol analogues as general anaesthetics using a tadpole in vivo assay. Both 2,6-diisopropylcyclohexanol and 2,6-dimethylcyclohexanol were effective as anaesthetics with EC(50)s of 14.0 muM and 13.1 muM respectively, while other cyclohexanols with bulkier side chains were less potent. In conclusion, our data indicate that cyclohexanols are both positive modulators of GABA(A) receptors currents and anaesthetics. The positioning and size of the alkyl groups at the 2 and 6 positions on the cyclohexanol ring were critical determinants of activity.  
  Call Number Serial 509  
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