The Peptides Mimicking the Third Intracellular Loop of 5-Hydroxytryptamine Receptors of the Types 1B and 6 Selectively Activate G Proteins and Receptor-Specifically Inhibit Serotonin Signaling via the Adenylyl Cyclase System

Шпаков, А. О.; Shpakova, E. A.; Tarasenko, I. I.; Derkach, K. V.; Vlasov, G. P.

doi:10.1007/s10989-010-9208-x

Cited by 62 publications

(39 citation statements)

References 38 publications

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“…e tissues were cut into small pieces; homogenized with a Polytron in 20 volumes of ice-cold 40 mM Tris-HCl buffer (pH 7.4) containing 5 mM MgCl 2 , 320 mM sucrose, and a cocktail of protease inhibitors 500 μM O-fenantrolin, 2 μM pepstatin, and 1 mM phenylmethylsulfonyl �uoride (Buffer A); and centrifuged at 480 ×g for 10 min at 4 ∘ C. e pellet was discarded, and the supernatant was centrifuged at 27 500 ×g for 20 min at 4 ∘ C. e pellet was resuspended in Buffer A (without sucrose) and then centrifuged at 27 500 ×g for 20 min. e preparation of synaptosomal membranes from the rat brain was performed as described earlier [22]. e brain tissues were dissected on ice and homogenized with a Polytron in 30 volumes of ice-cold 50 mM Tris-HCl buffer (pH 7.4) containing 10 mM MgCl 2 , 2 mM EGTA, 10% (w/v) sucrose, and a cocktail of protease inhibitors (Buffer B).…”

Section: Methodsmentioning

confidence: 99%

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Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

Шпаков

Derkach

Moyseyuk

et al. 2013

Dataset Papers in Pharmacology

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One of the causes of complications in type 1 diabetes mellitus (T1DM) is the changes in adenylyl cyclase (AC) signaling system, identi�ed on the early stages of the disease. However, the most signi�cant disturbances in this system occur on the later stages of T1DM, which ultimately leads to severe complications, but functional state of the AC system in late T1DM is poorly understood. e aim of this work was to study alterations in AC system sensitive to biogenic amines and polypeptide hormones in the heart, brain, and testes of male rats with long-term, 7-month, streptozotocin T1DM and to assess the in�uence on them of 135-day therapy with intranasal insulin. It was shown that AC effects of -adrenergic agonists in the heart, serotonin receptor agonists and PACAP-38 in the brain, chorionic gonadotropin and PACAP-38 in the testes, and somatostatin in all investigated tissues in long-term T1DM were drastically decreased. e treatment with intranasal insulin (0.48 IU/day) signi�cantly restored these effects. e results were obtained suggesting that long-term T1DM induces signi�cant alterations in hormone-sensitive AC system in the heart, brain, and testes that are much more pronounced, compared with short-term T1DM, and include a large number of hormonal regulations.

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Section: Methodsmentioning

confidence: 99%

“…e adenylyl cyclase (AC, EC 4.6.1.1) activity was measured as described previously [22]. e reaction mixture (�nal volume 50 μL) contained 50 mM Tris-HCl (pH 7.5), 5 mM MgCl 2 , 1 mM ATP, 1 μCi [ -32 P]-ATP, 0.1 mM cAMP, 20 mM creatine phosphate, 0.2 mg/mL creatine phosphokinase, and 15-45 μg of membrane protein.…”

Section: Methodsmentioning

confidence: 99%

Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

Шпаков

Derkach

Moyseyuk

et al. 2013

Dataset Papers in Pharmacology

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“…The preparation of synaptosomal membranes from the rat brain was performed as described earlier [21]. The brain tissues were dissected on ice and homogenized with a Polytron in 30 volumes of icecold 50 mM Tris-HCl buffer (pH 7.4) containing 10 mM MgCl 2 , 2 mM EGTA, 10% (w/v) sucrose and a cocktail of protease inhibitors (Buffer B).…”

Section: Plasma Membrane Preparationmentioning

confidence: 99%

Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes

Chistyakova

Derkach

et al. 2011

Open Life Sciences

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Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes Abbreviations:AC -adenylyl cyclase; AC system -adenylyl cyclase signaling system; DM -diabetes mellitus; EMD-386088 -5 -c h l o r o -2 -m e t h y l -3 -( 1 , 2 , 3 , 6 -tetrahydro-4-pyridinyl)-1H-indole; GppNHp -b,g-imidoguanosine-5'-triphosphate; 5-HT receptor -5-hydroxytryptamine receptor; hCG -human chorionic gonadotropin; PACAP-38 -pituitary adenylyl cyclase-activating peptide-38. IntroductionHypertension, coronary heart diseases, atherosclerosis, nephropathy, retinopathy, neuropathy, cognitive deficit and disorders of the reproductive system are the most common complications of diabetes mellitus (DM) [1][2][3]. Chronic hyperglycemia is quite often an important contributing factor in the development of these complications. Many hormone-and growth factorregulated signaling pathways, such as the adenylyl cyclase (AC) signaling system, phospholipase C/protein kinase C signaling system and the cascade of mitogenactivated protein kinases are implicated in the regulation of the cardiovascular, nervous and reproductive systems and aberration of their functional activity in DM may contribute to complications of this disease [4][5][6][7][8]. It has been shown that in experimental types 1 and 2 DM the functional activity of hormone-sensitive AC system in the skeletal muscles, myocardium, testis, ovaries, uterus and brain of diabetic rats and the sensitivity of this system to hormones regulating AC activity are changed in tissue-and hormone-specific manner [6][7][8][9][10][11][12].The most significant changes of hormonal sensitivity of AC system were found in the myocardium, testis and Abstract:The changes in hormone-regulated adenylyl cyclase (AC) signaling system implicated in control of the nervous, cardiovascular and reproductive systems may contribute to complications of diabetes mellitus (DM). We investigated the functional state of AC system in the brain, myocardium, ovary and uterus of rats with neonatal DM and examined the influence of intranasally administered insulin on the sensitivity of this system to biogenic amines and polypeptide hormones. The regulatory effects of somatostatin and 5-HT 1B R-agonist 5-nonyloxytryptamine acting via G i protein-coupled receptors were significantly decreased in DM and partially restored in insulin-treated rats. The effects of hormones, activators of AC, are changed in tissue-and receptorspecific manner, and intranasal insulin restored the effects rather close to the level in control. In insulin-treated non-diabetic rats, AC stimulating effects of isoproterenol and relaxin in the myocardium and of human chorionic gonadotropin in the ovaries were decreased, while the effects of hormones, inhibitors of AC, were increased. These data indicate that with intranasal insulin, G i protein-mediated signaling pathways continue to gain strength. The obtained data on the influence of hormones on AC system in the brain, myocardium, ovary and uterus allow looking anew into the mechanisms of therapeutic ...

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“…Имеется много работ, авторы которых показали, что пептиды, соответствующие ЦП рецепторов, регулирующих эндокринные функции организма, активны in vitro и селективно влияют на гормональные сигнальные системы [37][38][39][40][41][42][43][44][45][46][47]. В большинстве своем они не содержат гидрофобных радикалов, и не могут быть отнесены к пепдуцинам.…”

Section: влияние на эндокринные системыunclassified

Prospects for use of peptides and their derivatives, structurally corresponding to the G protein-coupled receptors, in medicine

Шпаков

Shpakova

2015

BIOMED KHIM

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The regulation of signaling pathways involved in the control of many physiological functions is carried out via the heterotrimeric G protein-coupled receptors (GPCR). The search of effective and selective regulators of GPCR and intracellular signaling cascades coupled with them is one of the important problems of modern fundamental and clinical medicine. Recently data suggest that synthetic peptides and their derivatives, structurally corresponding to the intracellular and transmembrane regions of GPCR, can interact with high efficiency and selectivity with homologous receptors and influence, thus, the functional activity of intracellular signaling cascades and fundamental cellular processes controlled by them. GPCR-peptides are active in both in vitro and in vivo. They regulate hematopoiesis, angiogenesis and cell proliferation, inhibit tumor growth and metastasis, and prevent the inflammatory diseases and septic shock. These data show greatest prospects in the development of the new generations of drugs based on GPCR-derived peptides, capable of regulating the important functions of the organism.

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The Peptides Mimicking the Third Intracellular Loop of 5-Hydroxytryptamine Receptors of the Types 1B and 6 Selectively Activate G Proteins and Receptor-Specifically Inhibit Serotonin Signaling via the Adenylyl Cyclase System

Cited by 62 publications

References 38 publications

Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

Alterations of Hormone-Sensitive Adenylyl Cyclase System in the Tissues of Rats with Long-Term Streptozotocin Diabetes and the Influence of Intranasal Insulin

Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes

Prospects for use of peptides and their derivatives, structurally corresponding to the G protein-coupled receptors, in medicine

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