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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) Lagostena, L.; Danober, L.; Challal, S.; Lestage, P.; Mocaer, E.; Trocme-Thibierge, C.; Cherubini, E. file  url
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  Title Modulatory effects of S 38232, a non alpha-7 containing nicotine acetylcholine receptor agonist on network activity in the mouse hippocampus Type Journal Article
  Year 2010 Publication Neuropharmacology Abbreviated Journal Neuropharmacology  
  Volume 58 Issue 4-5 Pages 806-815  
  Keywords Animals; Cholinergic Agonists/pharmacology; Dose-Response Relationship, Drug; Excitatory Postsynaptic Potentials/drug effects/physiology; Female; Hippocampus/*drug effects/physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Net/*drug effects/physiology; Nicotinic Agonists/*pharmacology; Rats; *Receptors, Nicotinic/physiology; Torpedo; Xenopus laevis; alpha7 Nicotinic Acetylcholine Receptor  
  Abstract Extracellular field potentials (fEPSPs) and whole cell patch-clamp recordings were used to test the effect of S 38232, a newly developed potent non-alpha7 nicotinic acetylcholine receptors (nAChR) agonist, on synaptic transmission in hippocampal slices obtained from adult mice. S 38232 increased the amplitude of fEPSPs, evoked in stratum radiatum by Schaffer collateral stimulation. This effect was potentiated by picrotoxin, suggesting that S 38232 exerts at least in part its effect on GABAergic interneurons. The action of S 38232 was mediated by non-alpha7 containing nAChRs since it was prevented by DHbetaE (1muM) but not by alpha-BTX (100nM). A similar potentiating effect on fEPSPs was observed when nicotine (1muM) was applied to hippocampal slices obtained from alpha7 -/- mice in the presence of picrotoxin. The potentiating effect of S 38232 was probably presynaptic in origin since it was associated with a significant reduction in paired-pulse ratio. In addition, in patch clamp experiments, S 38232 enhanced the frequency (but not the amplitude) of spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs, sIPSCs) recorded from CA1 principal cells. Moreover, it enhanced the frequency of miniature IPSCs but not EPSCs, suggesting that it was acting on nAChRs located on presynaptic/pre-terminal regions of GABAergic interneurons. The effect of S 38232 on GABAergic signaling was concentration-dependent with an EC(50) of 43muM. In conclusions, we present evidence that the new nicotine ligand S 38232, by selectively activating non-alpha7 nAChRs located on principal cells and GABAergic interneurons, influences network activity and information processing in the hippocampus.  
  Call Number Serial 1082  
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