Skip to main content
SpringerLink
Log in

Effect of Endogenous Neuropeptide Cycloprolylglycine on GABAA Receptors in Cerebellar Purkinje Cells

  • PHARMACOLOGY AND TOXICOLOGY
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

Voltage clamp and concentration-jump methods were employed to examine the effects of endogenous neuropeptide cycloprolylglycine on GABA-activated ionic currents in isolated cerebellar Purkinje cells. In the concentration range of 0.1-10.0 μM, short-term (600 msec) external application of cycloprolylglycine against the background of GABA-evoked current produced no effect on its amplitude. In contrast, application of 1 μM cycloprolylglycine increased current up to 177±15% control level. The development of potentiating effect and return to the control level of ionic current were slow, which was indicative of possible implication of second messenger systems in these processes. Functional augmentation of GABAA receptors under the action of cycloprolylglycine can underlie the established neuroprotective and anxiolytic effects of this endogenous dipeptide.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ashmarin IP, Koroleva SV, Myasoedov NF. Synactones – functionally conjugated complexes of endogenous regulators. Eksp. Klin. Farmakol. 2006;69(5):3-6. Russian.

    CAS  PubMed  Google Scholar 

  2. Gudasheva TA. Theoretical grounds and technologies for dipeptide drug development. Russ. Chem. Bull. 2015;64(9):2012-2021.

    Article  CAS  Google Scholar 

  3. Gudasheva TA, Vasilevich NI, Zolotov NN, Lezina VP, Rozenberg SG, Kravchenko EV, Ostrovskaya RU, Voronina TA, Rozantsev GG, Skoldinov AP. On the mechanism of nootropic action of topological analogues of piracetam based on proline. Khim.-Farm. Zh. 1991;25(6):12-15. Russian.

    CAS  Google Scholar 

  4. Gudasheva TA, Koliasnikova KN, Seredenin SB, Grigoriev VV, Zamoyski VL. Neuropeptide cycloprolylglycine is an endogenous positive modulator of AMPA receptors. Doklady Biochem. Biophysics. 2016;471(1):387-389.

    Article  CAS  Google Scholar 

  5. Kolyasnikova KN, Gudasheva TA, Nazarova GA, Antipov PI, Nikolaev SV, Antipova TA, Voronina TA, Seredenin SB. Similarity of Cycloprolylglycine to Piracetam in Antihypoxic and Neuroprotective Effects. Eksp. Klin. Farmakol. 2012;75(9):3-6. Russian.

    CAS  Google Scholar 

  6. Shuvaev AN, Salmin VV, Kuvacheva NV, Pozhilenkova EA, Salmina AB. Current trends in the development of the method of local potential fixation: new opportunities for neuropharmacology and neurobiology. Annaly. Klin. Eksp. Nevrol. 2015;9(4):54-58. Russian.

    Google Scholar 

  7. Faden AI, Knoblach SM, Movsesyan VA, Lea PM 4th, Cernak I. Novel neuroprotective tripeptides and dipeptides. Ann. NY Acad. Sci. 2005;1053:472-481.

    Article  CAS  PubMed  Google Scholar 

  8. Ferro JN, de Aquino FL, de Brito RG, dos Santos PL, Quintans J de S, de Souza LC, de Araújo AF, Diaz BL, Lucca-Júnior W, Quintans-Júnior LJ, Barreto E. Cyclo-Gly-Pro, a cyclic dipeptide, attenuates nociceptive behaviour and inflammatory response in mice. Clin. Exp. Pharmacol. Physiol. 2015;42(12):1287-1295.

    Article  CAS  PubMed  Google Scholar 

  9. Guan J, Harris P, Brimble M, Lei Y, Lu J, Yang Y, Gunn AJ. The role for IGF-1-derived small neuropeptides as a therapeutic target for neurological disorders. Expert Opin. Ther. Targets. 2015;19(6):785-793.

    Article  CAS  PubMed  Google Scholar 

  10. Gudasheva TA, Boyko SS, Akparov VKh, Ostrovskaya RU, Skoldinov SP, Rozantsev GG, Voronina TA, Zherdev VP, Seredenin SB. Identification of a novel endogenous memory facilitating cyclic dipeptide cyclo-prolylglycine in rat brain. FEBS Lett. 1996;391(1-2):149-152.

    Article  CAS  PubMed  Google Scholar 

  11. Gudasheva TA, Boyko SS, Ostrovskaya RU, Voronina TA, Akparov VK, Trofimov SS, Rozantsev GG, Skoldinov AP, Zherdev VP, Seredenin SB. The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine. Eur. J. Drug Metab. Pharmacokinet. 1997;22(3):245-252.

    Article  CAS  PubMed  Google Scholar 

  12. Gudasheva TA, Ostrovskaya RU, Trofimov SS, Sosoi MYu, Ienkina FV, Burov YuV, Soldinov AP. Peptide analogs of pyracetam as ligands for hypothetical nootropic receptors. Pharm. Chem. J. 1985;19(11):762-769.

    Article  Google Scholar 

  13. Gudasheva TA, Voronina TA, Ostrovskaya RU, Rozantsev GG, Vasilevich NI, Trofimov SS, Kravchenko EV, Skoldinov AP, Seredenin SB. Synthesis and antiamnesic activity of a series of N-acylprolyl-containing dipeptides. Eur. J. Med. Chem. 1996;31(2):151-157.

    Article  CAS  Google Scholar 

  14. Nakamura Y, Darnieder LM, Deeb TZ, Moss SJ. Regulation of GABAARs by phosphorylation. Adv. Pharmacol. 2015;72:97-146.

    Article  CAS  PubMed  Google Scholar 

  15. Porcher C, Hatchett C, Longbottom RE, McAinch K, Sihra TS, Moss SJ, Thomson AM, Jovanovic JN. Positive feedback regulation between gamma-aminobutyric acid type A (GABA(A)) receptor signaling and brain-derived neurotrophic factor (BDNF) release in developing neurons. J. Biol. Chem. 2011;286(24):21 667-21 677.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Center of Neurology, Moscow, Russia

    I. N. Sharonova, Yu. V. Bukanova & V. G. Skrebitsky

  2. V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia

    T. A. Gudasheva

Authors
  1. I. N. Sharonova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu. V. Bukanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. A. Gudasheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. G. Skrebitsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. N. Sharonova.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 1, pp. 42-45, January, 2019

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharonova, I.N., Bukanova, Y.V., Gudasheva, T.A. et al. Effect of Endogenous Neuropeptide Cycloprolylglycine on GABAA Receptors in Cerebellar Purkinje Cells. Bull Exp Biol Med 167, 39–42 (2019). https://doi.org/10.1007/s10517-019-04455-7

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-019-04455-7

Key Words

Search

Navigation