Scientific Notes of V.I. Vernadsky Crimean Federal University. Biology. Chemistry Scientific Notes of V.I. Vernadsky Crimean Federal University. Biology. Chemistry Ученые записки Крымского федерального университета имени В.И. Вернадского. Биология. Химия. 2413-1725 100848 10.29039/2413-1725-2025-11-2-85-98 БИОЛОГИЧЕСКИЕ НАУКИ BIOLOGICAL SCIENCES БИОЛОГИЧЕСКИЕ НАУКИ RESPIRATORY REACTIONS TO ADENOSINE TRIPHOSPHATE ADMINISTRATION IN THE AREA OF THE RETROTRAPEZIOID NUCLEUS IN RATS РЕСПИРАТОРНЫЕ РЕАКЦИИ НА ВВЕДЕНИЕ АДЕНОЗИНТРИФОСФАТА В ОБЛАСТЬ РЕТРОТРАПЕЦИЕВИДНОГО ЯДРА У КРЫС Конашенкова А. Т. Konashenkova A. T. Ведясова О. А. Vedyasova O. A. Инюшкин А. Н. Inyushkin A. N. Самарский национальный исследовательский университет имени академика С.П. Королева Samara University 04 07 2025 04 07 2025 11 2 85 98 02 07 2025 https://sn-biolchem.cfuv.ru/респираторные-реакции-на-введение-ад/

Ретротрапециевидное ядро (РТЯ) играет ключевую роль в центральной хеморецепции, участвует в регуляции дыхания, обеспечивая центральный респираторный хеморефлекс в ответ на гиперкапнию и гипоксию. Активность нейронов РТЯ контролируется многими нейромедиаторными системами, среди которых до конца не установлена роль пуринергических механизмов. В настоящем исследовании изучены изменения паттерна внешнего дыхания и биоэлектрической активности диафрагмальной мышцы при микроинъекциях АТФ, как агониста Р2-рецепторов, в область РТЯ у наркотизированных крыс, дышащих атмосферным воздухом неизмененного газового состава. Показано, что в этих условиях воздействие АТФ на РТЯ усиливает внешнее дыхание и стимулирует инспираторную залповую активность диафрагмы. Полученные данные указывают на участие пуринергической системы, в частности Р2-рецепторов РТЯ, в регуляции дыхания в условиях нормоксии.

The research of neurochemical mechanisms of respiratory regulation is very relevant, which is due to the need for further development of ideas about the role of various parts of the central respiratory neural network in the generation of breathing rhythm and pattern. In this aspect, the retrotrapezoid nucleus (RTN) is of interest, which is the main chemosensory structure of the medulla and provides the central chemoreflex under conditions of hypercapnia and hypoxia. Various neurotransmitters, including adenosine triphosphate (ATP), participate in the modulation of respiration at the RTN level. It is known that ATP provides purinergic signaling in the RTN during hypercapnia and hypoxia. However, under normoxia, the role of ATP in the regulation of respiration by RTN structures not been sufficiently studied. The aim of our research was to analyze the participation of ATP, as an agonist of purinergic receptors, in the mechanisms of respiratory control at the level of the RTN in rats breathing normal atmospheric air. The reasearch performed on adult rats weighing 180-220 g, anesthetized with urethane, in which the respiratory effects of microinjections of an ATP solution into the RTN were studied. Microinjections were carry out through a glass microcannula (tip diameter 30-50 μm), introduced into the brain according to stereotaxic coordinates. Control animals were injected with artificial cerebrospinal fluid into the RTN. In rats, the external respiration pattern was recorded using a spirograph connected to a tracheostomy tube, and simultaneously bioelectrical activity of the diaphragm was recorded on an electromyograph by bipolar needle electrodes Changes in frequency and volume parameters of spirogram and electromyogram (EMG) were analyzed. It has been established that microinjections of ATP into the RTN increase the respiratory activity of rats breathing atmospheric air of normal composition, as evidenced by changes in external respiration and EMG of the diaphragm. Analysis of spirogram revealed an increase in the respiratory rate (due to a decrease in the duration of inspiration and expiration), an increase in tidal volume, volumetric rate of inspiratory flow and minute lung ventilation compared to the initial level and control. Microinjections of ATP into the RTN also had a stimulating effect on the bioelectrical activity of the diaphragmatic muscle. The EMG showed an increase in the frequency of inspiratory burst discharges in combination with a decrease in the duration of both, the themselves bursts and interbursts intervals, relative to the initial values. These effects were accompanied by an increase in the amplitude of oscillations in inspiratory discharges. The observed reactions of the diaphragm statistically significantly exceeded the changes in control rats. The obtained results fit into the framework of the concept that activation of purine receptors in the medulla oblongata stimulates motor inspiratory output from the respiratory center. Taking into account the literature data, the increase in lung ventilation and bioelectrical activity of the diaphragm in response to ATP microinjections into the RTN may be explained by the activation of P2Y-type purinergic receptors. Thus, data obtained confirming the participation of the purinergic system at the level of the RTN in the respiration control in rats breathing atmospheric air of normal composition. Based on the analysis of our own and literary data, the assessment of the molecular mechanisms of action of ATP, as the most important component of the purinome, allows us to conclude that P2Y receptors play an important role in the implementation of the respiratory effects of ATP in the RTN area. The interaction of ATP with receptors of this type in the RTN region causes stimulation of external respiration and inspiratory burst activity of the diaphragmatic muscle, which indicates the contribution of purinergic signaling to the formation of inspiratory drive from the central respiratory neural network to respiratory motor neurons. It is noteworthy that the increase in respiration caused by the effect of ATP on the RTN is observed not only under conditions of altered gas homeostasis, as indicated by many publications, but also under normoxia, which is confirmed by our data. This fact allows us to consider the purinergic mechanisms of the RTN not only in the context of maintaining the body’s vital functions under hypoxic and hypercapnic conditions, but also in the aspect of regulating respiration under conditions of optimal gas balance.

 регуляция дыхания ретротрапециевидное ядро Р2-рецепторы аденозинтрифосфат (АТФ) микроинъекции внешнее дыхание электромиограмма диафрагмальной мышцы.

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