Proteolysis of His-Phe-Arg-Trp-Pro-Gly-Pro in the blood and brain of rats in vivo

Шевченко, К. В.; Nagaev, I. Yu.; Babakov, Vladimir; Андреева, Л. А.; Шевченко, В. П.; Radilov, A. S.; Myasoedov, N. F.

doi:10.1134/s1607672915050087

Cited by 7 publications

(4 citation statements)

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“…The effects observed after peptide administration may be the result of the action of the pool of peptides—the initial peptide and the products of its proteolytic degradation (synacton) (Vyunova et al, 2016). As a result of proteolysis of the peptides studied, different derivatives are formed, which may cause differences in their effects (Shevchenko et al, 2015; Zolotarev et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In the acute restraint stress model, we analyzed the delayed effect of peptides on the GABA‐receptor system, namely, after a sufficient time has elapsed for the peptide to reach its target in the brain, trigger cellular response processes and be destroyed by proteolytic enzymes. It was shown earlier that the peptides studied are able to entry into the brain after systemic administration, amount of the peptides in the brain reached its maximum in several minutes after injection, and then diminished at 1–2 h (Potaman et al, 1991; Shevchenko et al, 2014, 2015).…”

Section: Introductionmentioning

confidence: 89%

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Synthetic corticotropins and the GABA‐receptor system: Direct and delayed effects

et al. 2023

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The central effectors of the stress system are greatly interconnected and include, among others, a large group of peptides derived from proopiomelanocortin. In addition to natural corticotropins, a number of artificial molecules that contain some ACTH fragments in their structure are also referred to members of this family. Some of them possess a wide range of biological activity. The molecular mechanism underlying the biological activity of such peptides is partly based on allosteric modulation of various receptors. We analyzed the ability of some biologically active synthetic corticotropins (ACTH(4‐7)PGP, ACTH(6‐9)PGP, ACTH(7‐10)PGP), and glyproline PGPL to affect the GABA‐receptor system of rat brain. The effects of the peptides were studied in the isolated plasma membranes of brain cells, as well as after systemic peptide administration in the rat model of acute restraint stress. The delayed effect of stress or preadministration of each of the studied peptides on [3H]GABA binding was different for its high‐ and low‐affinity‐specific sites. The studied peptides individually affected the binding of [3H]GABA in their own way. Acute restraint stress caused a decrease in [3H]GABA binding at its low‐affine site and did not affected the high‐affine site. Preliminary peptide administration did not influence this effect of stress.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 89%

Synthetic corticotropins and the GABA‐receptor system: Direct and delayed effects

et al. 2023

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“…В основе центрального действия пептида могут находиться следующие механизмы. Так, АКТГ 6-9 -ПГП мог снижать активность гипоталамо-гипофизарно-надпочечниковой оси путем взаимодействия с центральными меланокортиновыми рецепторами вследствие его способности проникать через гематоэнцефалический барьер [19]. Данное обстоятельство может обусловить снижение секреции КРФ в гипоталамусе и, следовательно, АКТГ и глюкокортикоидов.…”

Section: Discussionunclassified

Effects of the ACTH<sup>6-9</sup>-Pro-Gly-Pro peptide on the morphofunctional state of rat colon under conditions of chronic restraint stress

et al. 2023

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Aim. To study the morphofunctional state of the colonic wall in rats when using the N–terminal analog of the adrenocorticotropic hormone (ACTH) ACTH6-9-Pro-Gly-Pro (ACTH6-9-PGP) peptide under chronic stress.Materials and methods. The study was performed on 55 male Wistar rats, which were divided into 5 groups (n = 11): group 1 – control group (administration of saline solution without stress); group 2 – chronic restraint stress (CRS) + administration of saline solution; group 3 – CRS + administration of ACTH6-9-PGP at a dose of 5 μg / kg; group 4 – administration of ACTH6-9-PGP at a dose of 50 μg / kg; group 5 – administration of ACTH6-9- PGP at a dose of 500 μg / kg. A histologic examination of the rat colon was performed. The histologic architecture of the colonic wall, the depth of crypts, and the number of goblet cells were assessed. Furthermore, the number of granulocytes, plasma cells, lymphocytes, macrophages, and mast cells was counted.Results. The study demonstrated that chronic (14 days) restraint stress resulted in the development of inflammations in the colonic wall of the animals. Intraperitoneal administration of ACTH6-9-PGP at doses of 50 and 500 μg / kg daily throughout the entire time of stress exposure prevented the development of stress-induced alterations observed in the control animals. At the same time, anti-inflammatory effects of the peptide in the colonic wall and a decrease in the level of corticosterone in the blood serum were noted.Conclusion. The results of this work and data from other studies on the effects of N-terminal analogs of ACTH indicate the need for studying the mechanisms of their effect on inflammation and searching for targets of ACTH6-9-PGP.

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“…The stability of ACTH(6–9)PGP and Semax is equivalent [ 19 ]. For both peptides, the ability to penetrate the blood-brain barrier and interact with brain structures has been established [ 20 , 21 , 22 ]. The polypeptide sequence of ACTH(6–9) is necessary and sufficient to activate most types of MC receptors [ 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Antistress Action of Melanocortin Derivatives Associated with Correction of Gene Expression Patterns in the Hippocampus of Male Rats Following Acute Stress

Filippenkov

Stavchansky

Glazova

et al. 2021

IJMS

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Natural melanocortins (MCs) have been used in the successful development of drugs with neuroprotective properties. Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4–7)PGP (Semax) and ACTH(6–9)PGP under normal and acute restraint stress (ARS) conditions. Administration of Semax or ACTH(6–9)PGP (100 μg/kg) to rats 30 min before ARS attenuated ARS-induced behavioral alterations. Using high-throughput RNA sequencing (RNA-Seq), we identified 1359 differentially expressed genes (DEGs) in the hippocampus of vehicle-treated rats subjected to ARS, using a cutoff of >1.5 fold change and adjusted p-value (Padj) < 0.05, in samples collected 4.5 h after the ARS. Semax administration produced >1500 DEGs, whereas ACTH(6–9)PGP administration led to <400 DEGs at 4.5 h after ARS. Nevertheless, ~250 overlapping DEGs were identified, and expression of these DEGs was changed unidirectionally by both peptides under ARS conditions. Modulation of the expression of genes associated with biogenesis, translation of RNA, DNA replication, and immune and nervous system function was produced by both peptides. Furthermore, both peptides upregulated the expression levels of many genes that displayed decreased expression after ARS, and vice versa, the MC peptides downregulated the expression levels of genes that were upregulated by ARS. Consequently, the antistress action of MC peptides may be associated with a correction of gene expression patterns that are disrupted during ARS.

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Proteolysis of His-Phe-Arg-Trp-Pro-Gly-Pro in the blood and brain of rats in vivo

Cited by 7 publications

References 3 publications

Synthetic corticotropins and the GABA‐receptor system: Direct and delayed effects

Synthetic corticotropins and the GABA‐receptor system: Direct and delayed effects

Effects of the ACTH<sup>6-9</sup>-Pro-Gly-Pro peptide on the morphofunctional state of rat colon under conditions of chronic restraint stress

Antistress Action of Melanocortin Derivatives Associated with Correction of Gene Expression Patterns in the Hippocampus of Male Rats Following Acute Stress

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