We studied the effects of intraperitoneal administration of L-arginine in doses of 5, 15, and 50 μg/kg and peptides in doses containing equimolar amount of this amino acid on aggressive-defensive behavior of rats (footshock model). The peptides were synthesized by binding of Pro-Gly-Pro sequence to one or both ends of the L-arginine molecule. The analgesic and antiagressogenic effects of L-arginine and opposite effects of arginine-containing peptides (except Pro-Gly-Pro tripeptide) were demonstrated. The combination of arginine with glyprolines yielded peptides with intrinsic regulatory properties. This expands the possibilities of synthesis of drugs for correction of pain and aggression caused by pain.
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References
Ashmarin IP. Glyproline in the composition of regulatory tripeptides. Neirokhimiya. 2007;24(1):5-7. Russian.
Butkevich IP, Mikhailenko VA. The damaging effects at an early age alter pain sensitivity in adult female rats, correction with buspirone. Ross. Fiziol. Zh. 2016;102(10):1146-1155. Russian.
V’yunova TV, Andreeva LA, Shevchenko KV, Shevchenko VP, Bobrov MYu, Bezuglov VV, Myasoedov NF. Peculiarities of specific binding of pentapeptide HFPGP labeled at the C-terminal proline residue with membranes of nerve cells in rat brain. Dokl. Akad. Nauk. 2014;456(4):490. Russian.
Zakutskii AN, Chalisova NI, Subbotina TF. Functional arginine-containing amino acid sequences in peptides and proteins. Russ. J. Bioorgan. Chem. 2008;34(2):135-144.
Medvedeva EV, Dmitrieva VG, Limborska SA, Myasoedov NF, Dergunova LV, Povarova OV, Skvortsova VI. Tripeptide Pro-Gly-Pro affects rat-brain transcriptome during focal ischemia. Mol. Biol. 2014;48(2):238-247.
Khavinson VKh, Soloviev AYu, Tarnovskaya SI, Lin’kova NS. The Mechanism of Short Peptides Biological Activity: Cell-Penetration and Epigenetic Regulation of Gene Expression. Uspekhi Sovremen. Biol. 2013;133(3):310-316. Russian.
Shevchenko KV, V’Yunova TV, Nagaev IYu, Andreeva LA, Myasoedov NF. Proteolysis of simple glyprolines by leucine aminopeptidase and enzymes from nasal mucus, brain membranes, and blood of rats. Russ. J. Bioorgan. Chem. 2013;39(3):283-287.
Bartus K, Pigott B, Garthwaite J. Cellular targets of nitric oxide in the hippocampus. PLoS One 2013;8(2):e57292. doi: https://doi.org/10.1371/journal.pone.0057292.
Futaki S, Suzuki T, Ohashi W, Yagami T, Tanaka S, Ueda K, Sugiura Y. Arginine-rich peptide. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J. Biol. Chem. 2001;276(8):5836-5840.
Gümrü S, Şahin C, Aricioğlu F. Role of agmatine in cognitive functions. OA Behav. Med. 2013;1(1):2.
Kawabata A, Umeda N, Takagi H. L-arginine exerts a dual role in nociceptive processing in the brain: involvement of the kyotophin-Met-encephalin and NO-cyclic gMP pathway. Br. J. Pharmacol. 1993;109(1):73-79.
Molderings GJ, Haenisch B. Agmatine (decarboxylated L-arginine): physiological role and therapeutic potential. Pharmacol. Ther. 2012;133(3):351-365.
Rodgers RJ, Semple JM. Pituitary-adrenocortical axis anduced fighting in rats. Physiol. Behav. 1978;20(5):533-537.
Sahin C, Albayrak O, Akdeniz T.F, Akbulut Z, Yanikkaya Demirel G, Aricioglu F. Agimatine reverses sub-chronic induced nod-like receptor protein 3 (NLRP3) activation and cytokine response in rats. Basic Clin. Pharmcol. Toxicol. 2016;119(4):367-375.
Sirvanci-Yalabik M, Sehirli AO, Utkan T, Aricioglu F. Agmatine, a metabolite of arginine, improves learning and memory in streptozotocin-induced Alzheimer’s disease model in rats. Bull. Clin Psychopharmacol. 2016;26(4):342-354. doi: https://doi.org/10.5455/bcp.20161121125642.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 165, No. 5, pp. 562-565, May, 2018
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Sever’yanova, L.А., Plotnikov, D.V. Binding of Glyprolines to L-Arginine Inverts Its Analgesic and Antiagressogenic Effects. Bull Exp Biol Med 165, 621–624 (2018). https://doi.org/10.1007/s10517-018-4227-2
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DOI: https://doi.org/10.1007/s10517-018-4227-2