Bulletin of Experimental Biology and Medicine

, Volume 164, Issue 5, pp 612–616 | Cite as

Modulation of GABA- and Glycine-Activated Ionic Currents with Semax in Isolated Cerebral Neurons

  • I. N. Sharonova
  • Yu. V. Bukanova
  • N. F. Myasoedov
  • V. G. Skrebitskii

The concentration-clamp experiments with neurons isolated from the rat brain showed that nootropic and neuroprotective drug Semax added to perfusion solution at concentration of 1 μM augmented the amplitude of GABA-activated ionic currents in cerebellum Purkinje cells by 147±13%. In addition, Semax in perfusion solution (0.1 and 1 μM) diminished the amplitude of glycine-activated chloride currents in hippocampal pyramidal neurons down to 68 and 43% control level, respectively. Both potentiating and inhibitory effects developed slowly, and they were poorly reversible, which indicated a probable implication of second messengers in the observed phenomena. Semax accelerated the falling edge of glycine-activated current both after a short-term co-application with agonist and after addition of this peptide into perfusion solution.

Key Words

Semax GABAA receptor glycine receptor cerebellum hippocampus 


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  1. 1.
    Ashmarin IP, Nezavibatko VN, Myasoedov NF, Kamensky AA, Grivennikov IA, Ponomareva-Stepnaya MA, Andreeva LA, Kaplan AY, Koshelev VB, Ryasina TV. Nootropic analogue of adrenocorticotropin 4-10-Semax: (the experience of design and investigation over 15 years). Zh. Vyssh. Nervn. Deyat. 1997;47(2):429-430. Russian.Google Scholar
  2. 2.
    V’unova TV, Shevchenko KV, Shevchenko VP, Bobrov MYu, Bezuglov VV, Myasoedov NF. Binding of Regulatory Neuropeptide [3H] Semax, Labeled in Terminal Pro, to Plasma Membranes of the Rat Forebrain. Neirokhimiya. 2006;23(1):57-62. Russian.Google Scholar
  3. 3.
    Gusev EI, Skvortsova VI, Myasoedov NF, Nezavibat’ko VN, Zhuravleva EYu, Vanichkin AV. Effectiveness of Semax in acute period of hemispheric ischemic stroke (clinical and electrophysiological study). Zh. Nevrol. Psikhiatr. 1997;96(6):26-54. Russian.Google Scholar
  4. 4.
    Gusev EI, Skvortsova VI, Chukanova EI. Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency. Zh. Nevrol. Psikhiatr. 2005;105(2):35-40.Google Scholar
  5. 5.
    Shuvaev AN, Salmin VV, Kuvacheva NV, Pozhilenkova EA, Salmina AB. Modern tendencies in the development of the patchclamp technique: new opportunities for neuropharmacology and neurobiology. Annaly Klin. Eksp. Nevrol. 2015;9(4):54-58. Russian.Google Scholar
  6. 6.
    Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol. Rev. 2004;56(1):1-29.CrossRefPubMedGoogle Scholar
  7. 7.
    Clarkson AN, Huang BS, Macisaac SE, Mody I, Carmichael ST. Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. Nature. 2010;468:305-309.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Cone RD. Anatomy and regulation of the central melanocortin system. Nat. Neurosci. 2005;8(5):571-578.CrossRefPubMedGoogle Scholar
  9. 9.
    Giuliani D, Ottani A, Neri L, Zaffe D, Grieco P, Jochem J, Cavallini GM, Catania A, Guarini S. Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives. Prog. Neurobiol. 2017;148:40-56.CrossRefPubMedGoogle Scholar
  10. 10.
    Hiu T, Farzampour Z, Paz JT, Wang EH, Badgely C, Olson A, Micheva KD, Wang G, Lemmens R, Tran KV, Nishiyama Y, Liang X, Hamilton SA, O’Rourke N, Smith SJ, Huguenard JR, Bliss TM, Steinberg GK. Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target. Brain. 2016;139(Pt 2):468-480.CrossRefPubMedGoogle Scholar
  11. 11.
    Lilly SM, Zeng XJ, Tietz EI. Role of protein kinase A in GABAA receptor dysfunction in CA1 pyramidal cells following chronic benzodiazepine treatment. J. Neurochem. 2003;85(4):988-998.CrossRefPubMedGoogle Scholar
  12. 12.
    McDonald BJ, Amato A, Connolly CN, Benke D, Moss SJ, Smart TG. Adjacent phosphorylation sites on GABAA receptor beta subunits determine regulation by cAMPdependent protein kinase. Nat. Neurosci. 1998;1(1):23-28.CrossRefPubMedGoogle Scholar
  13. 13.
    Nusser Z, Sieghart W, Mody I. Differential regulation of synaptic GABAA receptors by cAMP-dependent protein kinase in mouse cerebellar and olfactory bulb neurones. J. Physiol. 1999;521(Pt 2):421-435.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ono Y, Saitow F, Konishi S. Differential modulation of GABAA receptors underlies postsynaptic depolarization- and purinoceptor-mediated enhancement of cerebellar inhibitory transmission: a non-Stationary fluctuation analysis study. PLoS One. 2016;11(3):e0150636. doi: Scholar
  15. 15.
    Xu TL, Gong N. Glycine and glycine receptor signaling in hippocampal neurons: diversity, function and regulation. Prog. Neurobiol. 2010;91(4):349-361.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • I. N. Sharonova
    • 1
  • Yu. V. Bukanova
    • 1
  • N. F. Myasoedov
    • 2
  • V. G. Skrebitskii
    • 1
  1. 1.Research Center of NeurologyMoscowRussia
  2. 2.Institute of Molecular GeneticsRussian Academy of SciencesMoscowRussia

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