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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2007; 53(3): 31-37


The synthetic cannabinoid agonistwin 55,212-2 potentiates the ampli-tudes of glycine-activated currents.

N.M. Yatsenko, T.S. Tsintsadze, N.A. Lozovaya.

    Bogomoletz Institute of Physiology, National Academy ofScience of Ukraine, Kyiv


Abstract

Most of the pharmacological actions of cannabinoids are medi- ated by CB1 receptors. There is also evidence that these compounds can produce effects that are not mediated by the activation of identified cannabinoid receptors. Our data demon- strate that cannabinoids may directly affect the functioning of inhibitory glycine receptor (GlyR) channels. Here, we report that cannabinoid receptors agonist WIN 55,212-2, in a CB1 receptor independent manner, cause a significant potentiation of the amplitudes of glycine-activated currents (IGly) in acutely isolated hippocampal CA3 and CA1 pyramidal neurons. The maximal potentiation by this compound was observed at the lowest concentration of glycine; with increasing concentrations of glycine, the potentiation significantly decreased. Also WIN 55,212-2 significantly accelerated the desensitization of Gly-in- duced chloride current and significantly decreased the rise time. The effects of WIN 55,212-2 on IGly were not attenuated in the presence of CB1 receptor antagonist AM251, suggesting that CB1 receptor activation are not involved in action of cannabinoid on GlyRs. Altogether these data allow us to suggest the exist- ence of a CB1R independent action of cannabinoids directly on glycine-activated currents, representing a novel antinociceptive mechanism of this compounds.

References

  1. Akaike N., Kaneda M. Glycine–gated chloride current in acutely isolated rat hypothalamic neurons // J. Neurophysiol. – 1989. – 62, №6. – P. 1400–1409.
  2. Barann M., Molderings G., Bruss M. et al. Direct inhi- bition by cannabinoids of human 5–HT3A receptors: probable involvement of an allosteric modulatory site //Brit. J. Pharmacol. – 2002. – 137, №5. – P. 589–596.Синтетичний аналог канабіноїдів
  3. Bowen S. E., Wiley J. L., Balster R. L. The effects of abused inhalants on mouse behavior in an elevated plus–maze // Eur. J. Pharmacol. – 1996. – 312, №2. – P. 131–136.
  4. Bowen S. E., Wiley J. L., Evans E. B. et al. Functional observational battery comparing effects of ethanol, 1,1,1–trichloroethane, ether, and flurothyl // Neuro- toxicol. Teratol. – 1996. – 18, №5. – P. 577–585.
  5. Di Marzo V., Breivogel C. S., Tao Q. et al. Levels, metabolism, and pharmacological activity of ananda- mide in CB(1) cannabinoid receptor knockout mice: evidence for non–CB(1), non–CB(2) receptor–medi-ated actions of anandamide in mouse brain // J.Neurochem. – 2000. – 75, №6. – P. 2434–2444.
  6. Di Marzo V., Bisogno T., De Petrocellis L. Endocan- nabinoids: new targets for drug development // Curr. Pharm. Des. – 2000. – 6, №13. – P. 1361–1380.
  7. Diana M. A., Bregestovski P. Calcium and endocan- nabinoids in the modulation of inhibitory synaptic trans- mission // Cell Calcium. – 2005. – 37, №5. –P. 497–505.
  8. Evans E. B., Balster R. L. CNS depressant effects of volatile organic solvents // Neurosci. Biobehav. Rev. – 1991. – 15, №2. – P. 233–241.
  9. 9. Fan P. Cannabinoid agonists inhibit the activation of 5– HT3 receptors in rat nodose ganglion neurons // J. Neurophysiol. – 1995. – 73, №2. – P. 907–910.
  10. 10. Hales T. G., Lambert J. J. The actions of propofol on inhibitory amino acid receptors of bovine adreno- medullary chromaffin cells and rodent central neurones// Brit. J. Pharmacol. – 1991. – 104, №3. – P. 619–628.
  11. Hejazi N., Zhou C., Oz M. et al. Delta9–tetrahydro- cannabinol and endogenous cannabinoid anandamide directly potentiate the function of glycine receptors // Mol. Pharmacol. – 2006. – 69, №3. – P. 991–997.
  12. Iversen L., Chapman V. Cannabinoids: a real prospect for pain relief? // Curr. Opin. Neurobiol. – 2002. – 2, №1. – P. 50–55.
  13. Kneussel M., Betz H. Clustering of inhibitory neurotransmitter receptors at developing postsynaptic sites: the membrane activation model // Trends Neurosci.– 2000. – 23, №9. – P. 429–435.
  14. Kondratskaya E. L., Lishko P. V., Chatterjee S. S. et al. BN52021, a platelet activating factor antagonist, is a selective blocker of glycine–gated chloride channel //Neurochem. Int. – 2002. – 40, №7. – P. 647–653.
  15. Mascia M. P., Machu T. K., Harris R. A. Enhancement of homomeric glycine receptor function by long–chain alcohols and anaesthetics // Brit. J. Pharmacol. – 1996. –119, №7 . – P. 1331–1336.
  16. Mascia M. P., Mihic S. J., Valenzuela C. F. et al. A single amino acid determines differences in ethanol ac- tions on strychnine–sensitive glycine receptors // Mol. Pharmacol. – 1996. – 50, №2. – P. 402–406.
  17. Meier J. C., Henneberger C., Melnick I. et al. RNA editing produces glycine receptor alpha3(P185L), resulting in high agonist potency // Nat. Neurosci. –2005. – 8, №6. – P. 736–744.
  18. Mihic S. J. Acute effects of ethanol on GABAA and glycine receptor function // Neurochem. Int. – 1999. –35, №2. – P. 115–123.
  19. 19. Moser V. C., Balster R. L. Acute motor and lethal ef- fects of inhaled toluene, 1,1,1–trichloroethane, hal- othane, and ethanol in mice: effects of exposure dura-tion // Toxicol. Appl. Pharmacol. – 1985. – 77, №2. –P. 285–291.
  20. 20. Oliver D., Lien C. C., Soom M. et al. Functional conversion between A–type and delayed rectifier K+ channels by membrane lipids // Science – 2004. – 304,№5668. – P. 265–270.
  21. Oz M., Ravindran A., Diaz–Ruiz O. et al. The endog- enous cannabinoid anandamide inhibits alpha7 nico- tinic acetylcholine receptor–mediated responses in Xe- nopus oocytes // J. Pharmacol. Exp. Ther. – 2003. –306, №3. – P. 1003–1010.
  22. Oz M., Tchugunova Y. B., Dunn S. M. Endogenous cannabinoid anandamide directly inhibits voltage–depen- dent Ca(2+) fluxes in rabbit T–tubule membranes // Eur.J. Pharmacol. – 2000. – 404, №1–2. – P. 13–20.
  23. Pertwee R. G. Cannabinoid receptors and pain // Prog.Neurobiol. – 2001. – 63, №5. – P. 569–611.
  24. Venance L., Piomelli D., Glowinski J. et al. Inhibition by anandamide of gap junctions and intercellular calcium signalling in striatal astrocytes // Nature – 1995. – 376,№6541. – P. 590–594.
  25. Wood R. W., Coleman J. B., Schuler R. et al. Anticon- vulsant and antipunishment effects of toluene // J. Pharmacol. Exp. Ther. – 1984. – 230, №2. – P. 407–412.

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