vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biologyvestnik-bio-msu-963Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕRESEARCH ARTICLEПотенциация спонтанной секреции ацетилхолина в моторных синапсах мыши под действием 2-арахидоноилглицерина и анандамидаSpontaneous acetylcholine release potentiation induced by 2-arachidonoylglycerol and anandamide in mouse motor synapsesТарасоваЕ. О.TarasovaE. O.

Тарасова Екатерина Олеговна – кандидат биологических наук, старший научный сотрудник кафедры физиологии человека и животных биологического факультета

119234, Москва, Ленинские горы, д. 1, стр. 12

Department of Human and Animal Physiology, Biological Faculty

Leninskiye Gory, 1–12, Moscow, 119234

cate1990@list.ruХоткинаН. А.KhotkinaN. A.

Хоткина Наталья Александровна – магистр первого года обучения кафедры физиологии человека и животных биологического факультета

119234, Москва, Ленинские горы, д. 1, стр. 12

Department of Human and Animal Physiology, Biological Faculty

Leninskiye Gory, 1–12, Moscow, 119234

natashakhotkina@yandex.ruhttps://orcid.org/0000-0003-1963-1382ГайдуковА. Е.GaydukovA. E.

Гайдуков Александр Евгеньевич – кандидат биологических наук, ведущий научный сотрудник кафедры физиологии человека и животных биологического факультета

119234, Москва, Ленинские горы, д. 1, стр. 12

Department of Human and Animal Physiology, Biological Faculty

Leninskiye Gory, 1–12, Moscow, 119234

gaydukov@gmail.comБалезинаО. П.BalezinaO. P.

Балезина Ольга Петровна – доктор биологических наук, профессор кафедры физиологии человека и животных биологического факультета 

119234, Москва, Ленинские горы, д. 1, стр. 12

Department of Human and Animal Physiology, Biological Faculty

Leninskiye Gory, 1–12, Moscow, 119234

balezina@mail.ruМосковский государственный университет имени М.В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian Federation20210503202176139Copyright © Тарасова Е.О., Хоткина Н.А., Гайдуков А.Е., Балезина О.П., 20212021Тарасова Е.О., Хоткина Н.А., Гайдуков А.Е., Балезина О.П.Tarasova E.O., Khotkina N.A., Gaydukov A.E., Balezina O.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/963

Сравнивали изменения параметров миниатюрных потенциалов концевой пластинки (МПКП) диафрагмы мыши при экзогенной аппликации двух классических эндоканнабиноидов – 2-арахидоноилглицерина (2-AG) и анандамида (AEA). 2-AG (1 мкМ) вызывал постепенный (в течение 2 ч) прирост амплитуды МПКП на 50%, не влияя при этом на частоту спонтанной секреции ацетилхолина (АХ). Усиливающий секрецию эффект 2-AG предотвращался действием обратного агониста CB1-рецепторов АМ 251 или везамикола – блокатора везикулярного ацетилхолинового транспортера. АЕА (30 мкМ), напротив, не вызвал изменений амплитуды МПКП, но индуцировал медленно развивающийся прирост частоты МПКП на 75%. Вызываемая АЕА потенциация спонтанной секреции АХ предотвращалась АМ 251, а также блокированием Са2+-каналов L-типа нитрендипином (1мкМ) или ингибированием активности протеинкиназы А с помощью H89 (1 мкМ). Сделано заключение о способности как 2-AG, так и АЕА оказывать пресинаптическое усиливающее влияние на спонтанную секрецию АХ. Стимулирующие эффекты эндоканнабиноидов, несмотря на активацию ими одних и тех же CB1рецепторов, не перекрываются и направлены на увеличение либо размера квантов АХ (в случае 2-AG), либо частоты секреции АХ (в случае АЕА). Это позволяет предполагать вовлечение разных внутриклеточных мишеней и каскадов в разнонаправленные стимулирующие эффекты 2-AG и АЕА в моторных синапсах мыши.

We compared the changes in miniature endplate potential (MEPP) parameters of the mouse diaphragm caused by exogenous application of two classical endocannabinoids – 2-arachidonoylglycerol (2-AG) (1 μM) and anandamide (AEA) (30 μM). 2-AG caused a slowly developing stable increase in MEPP amplitude by 50%, without affecting the frequency of the MEPPs. This effect was prevented by AM-251, an inverse agonist of CB1-receptors, as well as by vesamicol, a blocker of the vesicular ACh transporter. On the contrary, AEA did not cause significant changes in the MEPP amplitude, but induced a slowly developing (within 2 hours) increase in MEPP frequency by on average 75%. The effect of AEA was prevented by AM-251 (1 μM) as well as by blocking of L-type Ca2+-channels with nitrendipine (1 μM) and inhibition of PKA activity by H89 (1 μM). We concluded that both 2-AG and AEA are able to exert a noncanonical facilitating presynaptic effect on spontaneous ACh release. Even though these endocannabinoids activate the same type of CB-receptors, their facilitating effects do not overlap and are strictly aimed either at potentiating the size of ACh quanta (in case of 2-AG) or increasing the frequency of MEPP (in case of AEA). We assume that different intracellular targets and signaling pathways may be involved in the differentiated facilitating effects of 2-AG and AEA in mouse neuromuscular junctions.

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