Inhibition of the hypercapnic ventilatory response by adenosine in the retrotrapezoid nucleus in awake rats.
Inhibition of the hypercapnic ventilatory response by adenosine in the retrotrapezoid nucleus in awake rats.
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DOI：
10.1016/j.neuropharm.2018.05.029
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发表时间：
2018-08
影响因子：
4.7
通讯作者：
Moreira TS
中科院分区：
文献类型：
--
作者：
Falquetto B;Oliveira LM;Takakura AC;Mulkey DK;Moreira TS
大脑通过一个被称为中枢化学接收的过程来调节呼吸，以响应组织中二氧化碳/氢离子的变化。后梯形核（RTN）中的神经元和星形胶质细胞具有呼吸化学感受器的功能。星形胶质细胞在这一过程中的作用似乎涉及CO2/H+依赖性ATP的释放，以增强化学敏感的RTN神经元的活性。考虑到在大多数大脑区域，胞外ATP通过外核苷酶活性迅速分解为腺苷，并且由于腺苷是一种有效的神经调节剂，我们想知道腺苷信号是否有助于RTN化学受体的功能。为了探索这种可能性，我们在对照条件下和吸入7-10%二氧化碳（高碳酸血症）时，从药理学上操纵RTN中腺苷受体的活性。在尿素麻醉或不受约束的清醒大鼠中，双侧向RTN注射腺苷可以减弱高碳酸血症的通气反应。腺苷对呼吸的抑制作用通过事先给RTN注射广谱腺苷受体阻滞剂（8-PT）或选择性a1受体阻滞剂（DPCPX）而减弱。尽管RTN注射8PT、DPCPX或外核苷酶抑制剂ARL67156对麻醉或清醒大鼠的基线呼吸没有影响。我们确实发现，在RTN中应用DPCPX或ARL67156增强了呼吸频率对CO2的反应，这表明在高CO2/H+时，RTN中释放的部分ATP转化为腺苷，并限制了化学受体的功能。这些结果确定腺苷是高碳酸血症期间RTN化学受体功能的一种新的嘌呤能调节剂。
The brain regulates breathing in response to changes in tissue CO2/H+ via a process called central chemoreception. Neurons and astrocytes in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors. The role of astrocytes in this process appears to involve CO2/H+-dependent release of ATP to enhance activity of chemosensitive RTN neurons. Considering that in most brain regions extracellular ATP is rapidly broken down to adenosine by ectonucleotidase activity and since adenosine is a potent neuromodulator, we wondered whether adenosine signaling contributes to RTN chemoreceptor function. To explore this possibility, we pharmacologically manipulated activity of adenosine receptors in the RTN under control conditions and during inhalation of 7–10% CO2 (hypercapnia). In urethane-anesthetized or unrestrained conscious rats, bilateral injections of adenosine into the RTN blunted the hypercapnia ventilatory response. The inhibitory effect of adenosine on breathing was blunted by prior RTN injection of a broad spectrum adenosine receptor blocker (8-PT) or a selective A1-receptor blocker (DPCPX). Although RTN injections of 8PT, DPCPX or the ectonucleotidase inhibitor ARL67156 did not affected baseline breathing in either anesthetized or awake rats. We did find that RTN application of DPCPX or ARL67156 potentiated the respiratory frequency response to CO2, suggesting a portion of ATP released in the RTN during high CO2/H+ is converted to adenosine and serves to limit chemoreceptor function. These results identify adenosine as a novel purinergic regulator of RTN chemoreceptor function during hypercapnia.
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DOI：
10.1126/science.1190721
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gourine AV;Kasymov V;Marina N;Tang F;Figueiredo MF;Lane S;Teschemacher AG;Spyer KM;Deisseroth K;Kasparov S
通讯作者：
Kasparov S
影响因子：
5.3
作者：
Guyenet, PG;Mulkey, DK;Bayliss, DA
通讯作者：
Bayliss, DA
影响因子：
16.2
作者：
Guyenet PG;Bayliss DA
通讯作者：
Bayliss DA
影响因子：
6.7
作者：
Fredholm, Bertil B.;Chern, Yijuang;Sitkovsky, Michail
通讯作者：
Sitkovsky, Michail
影响因子：
5.8
作者：
Funk, Gregory D.
通讯作者：
Funk, Gregory D.