Email this article 
The neuroprotective action of endocannabinoid N-arachidonoyldopamine (AA-DA) in the model of apoptosis induced in cultured rat cerebellar granule neurons by K+ deprivation was investigated. The efficacy of simultaneous application of AA-DA with fatty acid amide hydrolase inhibitor N-eicosapentaenoyldopamine (EPA-5HT) was also evaluated. It was shown that AA-DA dose-dependently protects neurons, with maximal effect of 65% survived cells observed at concentration 10 μM. The use of submaximal concentration (5 μM) of AA-DA in combination with EPA-5HT (10 μM) led to significant enhancement of neuroprotection. The value of cell survival for the combination exceeded such values for AA-DA alone in concentration of 5 and 10 μM, increasing the neuronal survival up to 78%. It may be concluded that such combination allows to reduce efficient concentration of neuroprotector and to diminish its possible side effects. Thus, the simultaneous application of endocannabinoid system modulators such as cannabinoid receptor agonists and inhibitors of endocannabinoid hydrolysis appears to be effective approach for neural cells protection.
Modulators of endogenous cannabinoid system аs neuroprotectors
- Authors: Genrikhs E.E.1, Bobrov M.Y.2, Andrianova E.L.1, Gretskaya N.M.3, Lyzhin A.A.1, Blazhenova A.V.3, Frumkina L.E.4, Bezuglov V.V.3, Khaspekov L.G.1
-
Affiliations:
- Research Center of Neurology
- Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Medical Sciences
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
- Research Center of Neurology, Russian Academy of Medical Sciences
- Issue: Vol 4, No 4 (2010)
- Pages: 37-42
- Section: Original articles
- URL: https://annaly-nevrologii.com/journal/pathID/article/view/323
- DOI: https://doi.org/10.17816/psaic323
- ID: 323
Cite item
Full Text
Abstract
About the authors
Elizaveta E. Genrikhs
Research Center of Neurology
Email: mbobr@mail.ru
Russian Federation, Moscow
M. Yu. Bobrov
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Medical Sciences
Email: mbobr@mail.ru
Russian Federation, Moscow
E. L. Andrianova
Research Center of Neurology
Email: mbobr@mail.ru
Russian Federation, Moscow
N. M. Gretskaya
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: mbobr@mail.ru
Russian Federation, Moscow
A. A. Lyzhin
Research Center of Neurology
Email: mbobr@mail.ru
Russian Federation, Moscow
A. V. Blazhenova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: mbobr@mail.ru
Russian Federation, Moscow
L. E. Frumkina
Research Center of Neurology, Russian Academy of Medical Sciences
Email: mbobr@mail.ru
Russian Federation, Moscow
V. V. Bezuglov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: mbobr@mail.ru
Russian Federation, Moscow
Leonid G. Khaspekov
Research Center of Neurology
Author for correspondence.
Email: mbobr@mail.ru
Russian Federation, Moscow
References
- Безуглов В.В., Грецкая Н.М., Блаженова А.В. и др. Арахидоноиламинокислоты и арахидоноилпептиды: синтез и свойства. Биоорган. химия 2006; 32: 258–267.
- Бобров М.Ю., Лыжин А.А., Андрианова Е.Л. и др. Антиоксидантные и нейропротекторные свойства N-докозагексаеноилдофамина. Бюл. эксп. биол. мед. 2006; 142: 406–408.
- Васильева Т.М., Петрухина Г.Н., Макаров В. А. и др. Влияние дофаминамидов полиненасыщенных жирных кислот на свертывающую систему крови и мозговое кровообращение. Эксп. клин. фармакол. 2002; 65: 41–45.
- Васильева Т.М., Петрухина Г.Н., Макаров В.А. и др. Действие ряда синтетических амидов арахидоновой и эйкозапентаеновой кислот на тромбоцитарную агрегацию. Пробл. гематологии и переливания крови 2005; 2: 15–21.
- Хаспеков Л. Г., Бобров М. Ю. Эндогенная каннабиноидная система и ее защитная роль при ишемическом и цитотоксическом повреждении нейронов головного мозга. Нейрохимия 2006; 23: 85–105.
- Andreeva N., Khodorov B., Stelmashook E. et al. Inhibition of Na+/Ca2+ exchange enhances delayed neuronal death elicited by glu tamate in cerebellar granule cell cultures. Brain Res. 1991; 548: 322–325.
- Bezuglov V., Bobrov M., Gretskaya N. et al. Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine. Bioorgan. Med. Chem. Lett. 2001; 11: 447–449.
- Bisogno T., Melck D., Bobrov M.Yu. et al. N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Biochem. J. 2000; 351: 817–824.
- Bisogno T., Melck D., De Petrocellis L. Arachidonoylserotonin and other novel inhibitors of fatty acid amide hydrolase. Biochem. Biophys. Res. Commun. 1998; 248: 515–522.
- Bobrov M., Gretskaya N., Payet O. et al. Different pharmacological profile of two closely related endocannabinoid ester analogs. Life Sci. 2005; 77: 1425–1440.
- Bobrov M.Y., Lizhin A.A., Andrianova E.L. et al. Antioxidant and neuroprotective properties of N-arachidonoyldopamine. Neurosci. Lett. 2008; 431: 6–11.
- Chu C.J., Huang S.M., De Petrocellis L. et al. N-oleoyldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia. J. Biol. Chem. 2003; 278: 13633–13639.
- De Petrocellis L., Chu C.J., Moriello A.S. et al. Actions of two naturally occurring saturated N-acyldopamines on transient receptor potential vanilloid 1 (TRPV1) channels. Br. J. Pharmacol. 2004; 143: 251–256.
- D’Mello S.R , Galli C., Ciotti T. Induction of apoptosis in cerebellar granule neurons by low potassium: inhibition of death by insulin-like growth factor I and cAMP. Proc. Natl. Acad. Sci. USA 1993; 90: 10989–10993.
- Fowler C.J., Tiger G., Lуpez-Rodrнguez M.L. et al. Inhibition of fatty acid amidohydrolase, the enzyme responsible for the metabolism of the endocannabinoid anandamide, by analogues of arachidonoyl-serotonin. J. Enzyme Inhib. Med. Chem. 2003; 18: 225–231.
- Hillard C.J., Wilkison D.M., Edgemond W.S. et al. Characterization of the kinetics and distribution of N-arachidonylethanolamine (anandamide) hydrolysis by rat brain. Biochim. Biophys. Acta. 1995; 1257: 249–256.
- Huang S.M., Bisogno T., Trevisani M. et al. An endogenous capsaicin- like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc. Natl. Acad. Sci. USA 2002; 99: 8400–8405.
- Mackie K. Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb. Exp. Pharmacol. 2005; 168: 299–326.
- Pandey R, Mousawy K, Nagarkatti M. et al. Endocannabinoids and immune regulation. Pharmacol. Res. 2009; 60: 85–92.
- Panikashvili D., Simeonidou C., Ben-Shabat S. et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001; 413: 527–531.
- Schomacher M., Mьller H.D., Sommer C. et al. Endocannabinoids mediate neuroprotection after transient focal cerebral ischemia. Brain Res. 2008; 1240: 213–220.
- Sinor A.D., Irvin S.M., Greenberg D.A. Endocannabinoids protect cerebral cortical neurons from in vitro ischemia in rats. Neurosci. Lett. 2000; 278: 157–160.
- Yates M.L., Barker E.L. Inactivation and biotransformation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol. Mol. Pharmacol. 2009; 76: 11–17.
Supplementary files
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).