Agmatin Biyokimyası: Şizofreni ve Depresyondaki Rolüne Bakış

Yıl 2019, Cilt: 9 Sayı: 2, 206 - 212, 28.06.2019

Erdem Çokluk , Ramazan Şekeroğlu , Emine Yılmaz

https://doi.org/10.31832/smj.461657

Öz

Agmatin imidazolin reseptör agonisti olup çok sayıda
reseptörle etkileşebilen nöroprotektif, anti-enflamatuvar, anti-stres,
anti-depresan özellikte, kognitif fonksiyonların düzenlenmesinde rol alan bir
moleküldür. Agmatinin beyindeki inaktivasyonu, reuptake mekanizmaları ve
enzimatik parçalanmayla gerçekleşmektedir. Gerialımı diğer
nörotransmitterlerden farklı olarak sıcaklığa bağlı gerçekleşmekte ve sadece
yüksek konsantrasyonlarda doygunluğa ulaşabilmektedir. Ayrıca, agmatinin
streste arttığı, dolayısıyla majör depresyon hastalarında akut dönemde tedavi
sonrası döneme göre plazma agmatin düzeylerinin daha yüksek olduğu da
bildirilmiştir. Bununla birlikte şizofreni gelişmeden önceki süreçte agmatin
eksikliğinden, şizofreni geliştikten sonraki dönemde ise agmatin artışından
bahseden çalışmalar da literatürde mevcuttur. Bu derlemede agmatinin
biyokimyası, şizofreni ve depresyondaki rolü ve 
nöroprotektif etkisi irdelenmiştir.

Anahtar Kelimeler

Agmatin, şizofreni, depresyon, nöroprotektif etki

Kaynakça

• 1. Bozkurt N I, Utkan T, Arıcıoğlu F, Agmatinin Kognitif Fonksiyonlara Etkisinin Araştırılması. MÜSBED, 2011.
• 2. Gerhard J. Molderings ⁎, Britta Haenisch, Agmatine (decarboxylated l-arginine): Physiological role and therapeutic potential, Pharmacology & Therapeutics 133 (2012) 351–365
• 3. Gümrü S, Şahin C, Arıcıoğlu F, Yeni bir nörotransmitter/nöromodülatör olarak agmatine genel bir bakış. MÜSBED 2013.
• 4. Reis D J,Regunathan S, Is agmatine a novel neurotransmitter in brain? Trends Pharmacol. Sci., 2000. 21(5): p. 187-193.
• 5. Piletz J E, Aricioglu F, Cheng J-T, Fairbanks C A, Gilad V H, Haenisch B, Halaris A, et al., Agmatine: clinical applications after 100 years in translation. Drug Discov Today, 2013. 18(17): p. 880-893.
• 6. Molderings G J,Haenisch B, Agmatine (decarboxylated l-arginine): Physiological role and therapeutic potential. Pharmacol Ther., 2012. 133(3): p. 351-365.
• 7. Halaris A,Plietz J, Agmatine. CNS drugs, 2007. 21(11): p. 885-900.
• 8. Uzbay T I, The pharmacological importance of agmatine in the brain. Neurosci Biobehav Rev., 2012. 36(1): p. 502-519.
• 9. Uzbay T, Nörokimyasal İletim, Biyolojik Psikiyatri, Işık E, Editor. 2012, Sigma Publishing: İstanbul. p. 44-45.
• 10. Uzbay T, Şizofreni Tedavisinde Yeni Bir Hedef Agmatin ve Beyin Poliamin Sistemi. Turk Psikiyatri Derg, 2009. 12(4).
• 11. Zhao S, Xie C, Lu X, Liu Y-M, Determination of agmatine in biological samples by capillary electrophoresis with chemiluminescence detection. Journal of Chromatography B, 2006. 832(1): p. 52-57.
• 12. Zhao S, Feng Y, LeBlanc M H, Piletz J E, Liu Y-M, Quantitation of agmatine by liquid chromatography with laser-induced fluorescence detection. Anal. Chim. Acta, 2002. 470(2): p. 155-161.
• 13. Cofre J, Montes P, Vallejos A, Benítez J, García D, Martínez-Oyanedel J, Carvajal N, et al., Further insight into the inhibitory action of a LIM/double zinc-finger motif of an agmatinase-like protein. J. Inorg. Biochem., 2014. 132: p. 92-95.
• 14. Demady D R, Jianmongkol S, Vuletich J L, Bender A T, Osawa Y, Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme. Mol. Pharmacol., 2001. 59(1): p. 24-29.
• 15. Su C-H, Liu I-M, Chung H-H, Cheng J-T, Activation of I 2-imidazoline receptors by agmatine improved insulin sensitivity through two mechanisms in type-2 diabetic rats. Neurosci. Lett., 2009. 457(3): p. 125-128.
• 16. Mun C H, Lee W T, Park K A, Lee J E, Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain. Anat Cell Biol, 2010. 43(3): p. 230-240.
• 17. Raasch W, Regunathan S, Li G, Reis D, Agmatine, the bacterial amine, is widely distributed in mammalian tissues. Life Sci., 1995. 56(26): p. 2319-2330.
• 18. Otake, K., Ruggiero, D.A., Regunathan, S., Wang, H., Milner, T.A., Reis, D.J., 1998. Regional localization of agmatine in the rat brain: an immunocytochemical study. Brain Res. 787 (1), 1–14.)
• 19. Peters, D., Berger, J., Langnaese, K., Derst, C., Madai, V.I., Krauss, M., Fischer, K.D., Veh, R.W., Laube, G., 2013. Arginase and arginine decarboxylase - where do the putative gate keepers of polyamine synthesis reside in rat brain? PLoS One 8 (6), e66735.
• 20. AndiaraE.Freitasa,b,n, VivianB.Neisb, AnaLúciaS.Rodriguesb Agmatine, a potential novel therapeutic strategy for depression European Neuropsychopharmacology(2016) 26, 1885–1899.
• 21. Pålsson E, Fejgin K, Wass C, Klamer D, Agmatine attenuates the disruptive effects of phencyclidine on prepulse inhibition. Eur. J. Pharmacol., 2008. 590(1): p. 212-216.
• 22. Uzbay T, Kayir H, Goktalay G, Yildirim M, Agmatine disrupts prepulse inhibition of acoustic startle reflex in rats. Hum Psychopharmacol, 2009.
• 23. Arıcıoğlu F, Agmatinin nöropsikiyatrideki yeri ve önemi RCHP 2009. 3(1-2): p. 7-14.
• 24. Jing Y, Zhang H, Wolff A R, Bilkey D K, Liu P, Altered arginine metabolism in the hippocampus and prefrontal cortex of maternal immune activation rat offspring. Schizophr Res, 2013. 148(1): p. 151-156.
• 25. Liu P, Jing Y, Collie N, Dean B, Bilkey D, Zhang H, Altered brain arginine metabolism in schizophrenia. Transl Psychiatry., 2016. 6(8): p. e871.
• 26. Stewart L S,McKay B, Acquisition deficit and time‐dependent retrograde amnesia for contextual fear conditioning in agmatine‐treated rats. Behav Pharmacol, 2000. 11(1): p. 93-97.
• 27. Aricioglu F,Altunbas H, Is agmatine an endogenous anxiolytic/antidepressant agent? Ann. N. Y. Acad. Sci., 2003. 1009(1): p. 136-140.
• 28. Zomkowski A D, Hammes L, Lin J, Calixto J B, Santos A R S, Rodrigues A L S, Agmatine produces antidepressant-like effects in two models of depression in mice. Neuroreport, 2002. 13(4): p. 387-391.
• 29. Zeidan M P, Zomkowski A D, Rosa A O, Rodrigues A L S, Gabilan N H, Evidence for imidazoline receptors involvement in the agmatine antidepressant-like effect in the forced swimming test. Eur. J. Pharmacol., 2007. 565(1): p. 125-131.
• 30. Budni J, Gadotti V M, Kaster M P, Santos A R, Rodrigues A L S, Role of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming test. Eur. J. Pharmacol., 2007. 575(1): p. 87-93.
• 31. Taksande B G, Kotagale N R, Tripathi S J, Ugale R R, Chopde C T, Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine. Neuropharmacol., 2009. 57(4): p. 415-424.
• 32. Bernstein H-G, Stich C, Jäger K, Dobrowolny H, Wick M, Steiner J, Veh R, et al., Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders. Neuropharmacol. , 2012. 62(1): p. 237-246.
• 33. Zhu M Y, Wang W P, Huang J, Regunathan S, Chronic treatment with glucocorticoids alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels. J. Neurochem., 2007. 103(5): p. 1811-1820.
• 34. Meylan E, Breuillaud L, Seredenina T, Magistretti P J, Halfon O, Luthi-Carter R, Cardinaux J, Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression. Transl Psychiatry., 2016. 6(7): p. e852.
• 35. Zhu M Y, Wang W P, Cai Z W, Regunathan S, Ordway G, Exogenous agmatine has neuroprotective effects against restraint‐induced structural changes in the rat brain. Eur. J. Neurosci., 2008. 27(6): p. 1320-1332.
• 36. Sevinç Ş S, Dalbudak E, Aldemir S, Özer İ, Akıncı Ş, Topcu M, Manic Episode Induced By Arginine, Lysine and Ornithine use. Psychopharmacol Bull, 2012. 22(1): p. S77.