clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2024-102-2-118-124clinmed-760Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESЛекарства — организаторы клеточных популяцийDrugs as organizers of cell populationsБродскийВ. Я.BrodskyV. Ya.

Всеволод Яковлевич Бродский — д-р биол. наук профессор

Москва

Vsevolod Ya. Brodsky, Doc. Biol. Sci., professor

Moscow

brodsky.vsevolod@mail.ruФГБУН Институт биологии развития им. Н.К. Кольцова РАНРоссияN.K. Koltsov’s Institute of Developmental Biology of the Russian Academy of SciencesRussian Federation2024080520241022118124Copyright © Бродский В.Я., 20242024Бродский В.Я.Brodsky V.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinmedjournal.com/jour/article/view/760

   Цель обзора — привлечь внимание к многостороннему биологическому действию лекарств, особенно к их влиянию на прямые межклеточные взаимодействия.

   Суммированы данные о том, что распространенные лекарства, такие как дофамин, глутаминовая кислота, мелатонин, средства, содержащие фенилэфрин, могут в зависимости от стимулированных рецепторов как организовать, так и дезорганизовать межклеточные связи. Действие можно предвидеть, учитывая сведения об агонизме или антагонизме влияния рецепторов на внутриклеточный кальций или цАМФ. Приводятся сведения о возможности купировать нежелательные эффекты. Суммированы данные о перспективах использования ганглиозидов в терапии.

   The aim of the review is to draw attention to the multifaceted biological action of medications, especially their infl uence on direct intercellular interactions.

   The data are summarized on the fact that common medications such as dopamine, glutamic acid, melatonin, phenylephrine-containing agents can, depending on the stimulated receptors, both organize and disorganize intercellular connections. The action can be predicted considering information on agonism or antagonism of receptor eff ects on intracellular calcium or cAMP. Information is provided on the possibility of mitigating unwanted eff ects. The data on the prospects of using gangliosides in therapy are summarized.

межклеточные взаимодействияфенилэфринмелатонинглутаминовая кислотадофаминганглиозидыпептидыintercellular interactionsphenylephrinemelatoninglutamic aciddopaminegangliosidespeptidesРабота включена в тему № 4 НИР ИБР РАН, номер ГЗ 0088-2021-0016, номер НИОКТР АААА-А21-121011490124-0The work is included in topic No. 4 of the research work of the IBR RAS, number GZ 0088-2021-0016, number NIOKTR AAAA-A21-121011490124-0ReferencesBrodsky V.Ya. Ultradian signals and direct cell-to-cell communication. 2022. M. Pero.Brodsky V.Ya. Ultradian signals and direct cell-to-cell communication. 2022. M. Pero.Kvetnoy I.M., Ingel I.E., Kvetnaya T.V., Malinovskaya N.K., Rapoport S.I., Raikhlin N.T., Trovimov A.V., Yuzakov V.V. Gasrointestinal melatonin. Cellular identifi cation and biological role. Neuroendocrinology Lett. 2002;23:121−132.Kvetnoy I.M., Ingel I.E., Kvetnaya T.V., Malinovskaya N.K., Rapoport S.I., Raikhlin N.T., Trovimov A.V., Yuzakov V.V. Gasrointestinal melatonin. Cellular identifi cation and biological role. Neuroendocrinology Lett. 2002;23:121−132.Заславская Р.М., Щербаков Е.А., Логвиненко С.И. Развитие различных методов лечения пациентов при стенокардии с гипертонией. Клиническая медицина. 2007;85(8):40−43.Zaslavskaya R.M., Tscherbakov E.A., Logvinenko S.I. Development of diff erent methods of therapy during stenocardia along hypertension. Klinicheskaya meditsina. 2007;85(8):40−43. (In Russian)Srinivasan V., Pandi-Perumal S.R., Maestroni G.J. Role of melatonin in neurodegenerative diseases. Neurotox. Res. 2005;7(4):293−318.Srinivasan V., Pandi-Perumal S.R., Maestroni G.J. Role of melatonin in neurodegenerative diseases. Neurotox. Res. 2005;7(4):293−318.Anisimov V.A., Egormin P.A., Piskunova T.S., Popovich I.G., Tyndyk M.L., Yurova M.N., Zabezhinski M.A., Anikin I.V., Karkach A.S, Romanyukha A.A. Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle. 2010;9(1):188–197.Anisimov V.A., Egormin P.A., Piskunova T.S., Popovich I.G., Tyndyk M.L., Yurova M.N., Zabezhinski M.A., Anikin I.V., Karkach A.S, Romanyukha A.A. Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle. 2010;9(1):188–197.Vinogradova I.A., Anisimov V.N., Bukalev A.V., Semenchenko A.V., Zabezhinski M.A. Circadian disruption induced by light at night accelerates aging and promotes tumorigenesis in rats. Aging. 2009;1(10):855−865.Vinogradova I.A., Anisimov V.N., Bukalev A.V., Semenchenko A.V., Zabezhinski M.A. Circadian disruption induced by light at night accelerates aging and promotes tumorigenesis in rats. Aging. 2009;1(10):855−865.Giannoulia-Karantana A., Vlachou A., Polychronopoulou S., Papassotiriou I., Chrousos G.P. Melatonin and immunomodu lation: connections and potential clinical applications. Neuroimmunomodulation. 2006;13(3):133−144.Giannoulia-Karantana A., Vlachou A., Polychronopoulou S., Papassotiriou I., Chrousos G.P. Melatonin and immunomodu lation: connections and potential clinical applications. Neuroimmunomodulation. 2006;13(3):133−144.Karasek M. Melatonin, human aging, and age-related diseases Exper. Gerontol. 2004;39:1723−1729.Karasek M. Melatonin, human aging, and age-related diseases Exper. Gerontol. 2004;39:1723−1729.Ledeen R.W., Wu G. Gangliosides, α-synuclein and Parkinson’s disease. PNAS. 2017;106:9483−9488.Ledeen R.W., Wu G. Gangliosides, α-synuclein and Parkinson’s disease. PNAS. 2017;106:9483−9488.Ledeen R.W., Wu G. The multi-tasked life of GM1 ganglioside, a true factotum of nature. Trends Biochem. Sci. 2015;1148:1−12.Ledeen R.W., Wu G. The multi-tasked life of GM1 ganglioside, a true factotum of nature. Trends Biochem. Sci. 2015;1148:1−12.Wu G, Lu Z-H, Kulkarni N, Amin R, Ledeen RW. Mice lacking major brain gangliosides develop parkinsonism. Neurochem. Res. 2011;36:1706−1714.Wu G, Lu Z-H, Kulkarni N, Amin R, Ledeen RW. Mice lacking major brain gangliosides develop parkinsonism. Neurochem. Res. 2011;36:1706−1714.Wu G., Lu Z-H., Kulkarni N., Ledeen R.W. Defficience of ganglioside GM1 correlates with Parkinson’s disease in mice and humans. J. Neurosci. Res. 2012;90:1997−2008.Wu G., Lu Z-H., Kulkarni N., Ledeen R.W. Defficience of ganglioside GM1 correlates with Parkinson’s disease in mice and humans. J. Neurosci. Res. 2012;90:1997−2008.Schneider J.S., Sendec S., Dascalakis C., Cambi F. (2010) GM1 ganglioside in Parkinson’s disease: results of a five year open study. J. Neurol.Sci. 2010;292:45−51.Schneider J.S., Sendec S., Dascalakis C., Cambi F. (2010) GM1 ganglioside in Parkinson’s disease: results of a five year open study. J. Neurol.Sci. 2010;292:45−51.Ladisch S. The role of tumor gangliosides in the immune distinctions of cancer. In: Cancer immunotherapy at the crossroad (J.H. Funke and R.M. Bukowski, eds.). Humana Press, Totowa, NY. 2004:145−156.Ladisch S. The role of tumor gangliosides in the immune distinctions of cancer. In: Cancer immunotherapy at the crossroad (J.H. Funke and R.M. Bukowski, eds.). Humana Press, Totowa, NY. 2004:145−156.Li R., Ladisch S. Inhibition of endogenous ganglioside synthesis does not block neurite formation by retinoic acid-treated neuroblastoma cells. J. Biol. Chem. 1997;272:1349−1354.Li R., Ladisch S. Inhibition of endogenous ganglioside synthesis does not block neurite formation by retinoic acid-treated neuroblastoma cells. J. Biol. Chem. 1997;272:1349−1354.Olshefski R., Ladisch S. Synthesis, shedding, and intracellular transfer of human medulloblastoma gangliosides: abrogation by new inhibitor of glycosylceramide synthase. J. Neurochem. 1998;70:467−472.Olshefski R., Ladisch S. Synthesis, shedding, and intracellular transfer of human medulloblastoma gangliosides: abrogation by new inhibitor of glycosylceramide synthase. J. Neurochem. 1998;70:467−472.Segui B., Andrie-Abadie N., Jaffrezou J., Benoist H., Levade T. Sphingolipids as modulators of cancer cell death. Bioch. Biophys. Acta. 2006;1758(12):2104−2120.Segui B., Andrie-Abadie N., Jaffrezou J., Benoist H., Levade T. Sphingolipids as modulators of cancer cell death. Bioch. Biophys. Acta. 2006;1758(12):2104−2120.Wen Deng, Li R., Ladisch S. Infl uence of cellular ganglioside depletion on tumor Formation. J. Natl. Cancer Inst. 2000;92:912–917.Wen Deng, Li R., Ladisch S. Infl uence of cellular ganglioside depletion on tumor Formation. J. Natl. Cancer Inst. 2000;92:912–917.Bergelson L.D., Dyatlovitskaya E.V., Klyuchareva T.E., Kryukova E.V., Lemenovskaya A.F., Matveeva V.A., Sinitsyna E.V. The role of glycosphingolipids in natural immunity. Gangliosides modulate the cytotoxicity of natural killer cells. Eur. J. Immunol. 1989;19:1979−1983.Bergelson L.D., Dyatlovitskaya E.V., Klyuchareva T.E., Kryukova E.V., Lemenovskaya A.F., Matveeva V.A., Sinitsyna E.V. The role of glycosphingolipids in natural immunity. Gangliosides modulate the cytotoxicity of natural killer cells. Eur. J. Immunol. 1989;19:1979−1983.Shaposhnikova G.I., Prokazova N.V., Buznikov G.A., Zvezdina N.D., Teplitz N.A., Bergelson L.D. (1984) Shedding of gangliosides from tumor cells depends on cell density. Europ. J. Biochem. 1984;140(3):567−570.Shaposhnikova G.I., Prokazova N.V., Buznikov G.A., Zvezdina N.D., Teplitz N.A., Bergelson L.D. (1984) Shedding of gangliosides from tumor cells depends on cell density. Europ. J. Biochem. 1984;140(3):567−570.Li R., Villacreses N., Ladisch S. Human tumor gangliosides inhibit murine immune responses in vivo. Cancer Res. 1995;55(2):211−214.Li R., Villacreses N., Ladisch S. Human tumor gangliosides inhibit murine immune responses in vivo. Cancer Res. 1995;55(2):211−214.Inokuchi J., Masayuki L., Momosaki K., Shimeno H., Nagamatsu A., Radin N.S. Inhibition of experimental metastasis of murine Lewis lung carcinoma by an inhibitor of glucosylceramide synthase and its possible mechanism of action. Cancer Res. 1990;50:6731−6737.Inokuchi J., Masayuki L., Momosaki K., Shimeno H., Nagamatsu A., Radin N.S. Inhibition of experimental metastasis of murine Lewis lung carcinoma by an inhibitor of glucosylceramide synthase and its possible mechanism of action. Cancer Res. 1990;50:6731−6737.Kyogashima M., Inouea M., Setoa A., Inokuchi J. Glucosylceramide synthetase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol exhibits a novel decarcinogenic activity against Shope carcinoma cells. Cancer Letters. 1996;10:25−30.Kyogashima M., Inouea M., Setoa A., Inokuchi J. Glucosylceramide synthetase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol exhibits a novel decarcinogenic activity against Shope carcinoma cells. Cancer Letters. 1996;10:25−30.Radin N.S. Rationales for cancer chemotherapy with PDMP, a specific inhibitor of glucosylceramide synthase. Mol. Chem. Neuropathol. 1994;21(2) :111−127.Radin N.S. Rationales for cancer chemotherapy with PDMP, a specific inhibitor of glucosylceramide synthase. Mol. Chem. Neuropathol. 1994;21(2) :111−127.Иванов А.В., Бобынцев И.И., Шепелева О.М., Крюков А.А., Андреева Л.А., Мясоедов Н.Ф. Влияние АКТГ-PGP (семакса) на морфофункциональное состояние гепатоцитов в условиях хронического эмоционально-болевого стресса. Бюл. эксп. биол. мед. 2017;163(1):123−127.Ivanov A.V., Bobianzev I.I., Myasoedov N.F. et al. Infl uence of AKTG-PDG (semax) on hepatocyte state under chronic emotional and painful stress. Bulletin of Experimental Biology and Medicine. 2017;161(1):123–127. (In Russian)Мясоедов Н.Ф., Гривенников И.А. Нейропептиды и их аналоги в регуляции функций нервной системы млекопитающих, включая человека. В книге «Проблемы и перспективы молекулярной генетики». М., Наука, 2004;195−236.Myasoedov N.F., Grivennikov I.A. Neuropeptides and their analogs on regulation of functions of nerve system of mammals including human. In: Problems and perspectives of the molecular genetics. M., Nauka, 2004;195−236. (In Russian)Dmitrieva V.G., Povarova O.V., Skvortsova V.I., Limborska S.A., Myasoedov N.F., Dergunova L.V. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell. Mol. Neurobiol. 2010;30(1):71−79.Dmitrieva V.G., Povarova O.V., Skvortsova V.I., Limborska S.A., Myasoedov N.F., Dergunova L.V. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell. Mol. Neurobiol. 2010;30(1):71−79.Золотарев Ю.А., Ковалев Г.И., Дадаян А.К., Козик В.С., Кондрахин Е.А., Васильева Е.В., Липкин В.М. Исследование фармакокинетики и фармакодинамики амидной формы нейропротекторного пептида HLDF-6. В кн. «Нейродегенеративные заболевания». М., Научный мир, 2014;763−777.Zolotarev Y.A., Kovalev G.I., Dadayan A.K. et al. Studies of farm kinetic and dynamic of the amid form the neuroprotector peptide HLDF-6. In: Neurodegenerative diseases. M., Nauchny Mir, 2014;763−777. (In Russian)Bogachouk A.P., Storozheva Z.I., Solovjeva O.A., Sherstnev V.V., Zolotarev Y.A., Azev V.N., Rodionov I.L., Surina E.A., Lipkin V.M. Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the HLDF-6 peptide in animal models of Alzheimer’s disease. J. Psychopharmacol. 2016;30(1):78−92.Bogachouk A.P., Storozheva Z.I., Solovjeva O.A., Sherstnev V.V., Zolotarev Y.A., Azev V.N., Rodionov I.L., Surina E.A., Lipkin V.M. Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the HLDF-6 peptide in animal models of Alzheimer’s disease. J. Psychopharmacol. 2016;30(1):78−92.Бродский В.Я., Золотарев Ю.А., Мальченко Л.А., Андреева Л.А., Лазарев Д.С., Буторина Н.Н., Козик В.С, Мясоедов Н.Ф. Нейропротекторные пептиды регулируют кинетику синтеза белка в гепатоцитах крыс разного возраста. Онтогенез. 2019;50(5):1−8.Brodsky V.Y., Zolotarev Y.A., Malchenko L.A., Myasiedov N.F. et al. Neuroprotector peptides regulate kinetic of protein synthesis in hepatocytes of rats of different ages. Ontogenez. 2019;50(5):1−8. (In Russian)Pytliak M., Vargova V., Mechirova V., Felsoci M. Serotonin receptors — from molecular biology to clinical applications. Physiol. Res. 2011;60:15−25.Pytliak M., Vargova V., Mechirova V., Felsoci M. Serotonin receptors — from molecular biology to clinical applications. Physiol. Res. 2011;60:15−25.Raymond J.R., Mukhin Y.V., Gelascoa A., Turnerb J., Collinswortha G., Gettysc T.W., Grewalb J.S., Garnovskaya M.N. Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacology and Therapeutics. 2001;92:179–212.Raymond J.R., Mukhin Y.V., Gelascoa A., Turnerb J., Collinswortha G., Gettysc T.W., Grewalb J.S., Garnovskaya M.N. Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacology and Therapeutics. 2001;92:179–212.Никишин Д.А., Семенова М.Н., Шмуклер Ю.Б. Экспрессия генов трансмиттерных рецепторов в раннем развитии морского ежа Paracentropus lividus. Онтогенез. 2012;43(3):212–216.Niki shin D.A., Semenova M.N., Shmukler Y.B. Expression of the transmitter receptors genes in early development of sea urchin Paracentropus lividus. Ontogenez. 2012;43(3):212–216. (In Russian)Никишин Д.А., Храмова Ю.В., Багаева Т.С., Семенова М.Л., Шмуклер Ю.Б. Экспрессия компонентов серотонинергической системы в фолликулогенезе и доимплантационном развитии мыши. Онтогенез . 2018;49(3):208–216.Nikishin D.A., Thramova Y.V., Shmukler Y.B. et al., Expression of serotonin system components by folliculogenesis and before implant development of mouse. Ontogenez. 2018;49(30):208–216 (In Russian)Abernethy D.R., Schwartz J.B. Calcium-antagonist drugs. N. Engl. J. Med. 1999;341:1447−1457.Abernethy D.R., Schwartz J.B. Calcium-antagonist drugs. N. Engl. J. Med. 1999;341:1447−1457.Lloyd D., Aon M.A., Cortassa S. Why homeodynamics not homeostasis? Sci. World. 2001;1:133−145.Lloyd D., Aon M.A., Cortassa S. Why homeodynamics not homeostasis? Sci. World. 2001;1:133−145.Yates F.E. Order and complexity in dynamical system: homeodynamics as a generalized mechanics for biology. Math. Comp. Model. 1994;19:49−74.Yates F.E. Order and complexity in dynamical system: homeodynamics as a generalized mechanics for biology. Math. Comp. Model. 1994;19:49−74.

The authors declare that there are no conflicts of interest present.