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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Inhibition of the hypercapnic ventilatory response by adenosine in the retrotrapezoid nucleus in awake rats

Texto completo
Autor(es):
Falquetto, Barbara [1] ; Oliveira, Luiz M. [1] ; Takakura, Ana C. [1] ; Mulkey, Daniel K. [2] ; Moreira, Thiago S. [3]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508 Sao Paulo, SP - Brazil
[2] Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 - USA
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508 Sao Paulo, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Neuropharmacology; v. 138, p. 47-56, AUG 2018.
Citações Web of Science: 1
Resumo

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 Al-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. (C) 2018 Elsevier Ltd. All rights reserved. (AU)

Processo FAPESP: 16/23281-3 - Regiões encefálicas responsáveis pela neuroplasticidade observada na resposta respiratória induzida por hipercapnia em modelo animal de doença de parkinson
Beneficiário:Ana Carolina Thomaz Takakura
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 15/23376-1 - Núcleo retrotrapezóide, quimiossensibilidade central e automaticidade respiratória
Beneficiário:Thiago dos Santos Moreira
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/22069-0 - Melhora nos mecanismos de regulação do fluxo sanguíneo encefálico em animais espontaneamente hipertensos: participação do exercício físico
Beneficiário:Thiago dos Santos Moreira
Linha de fomento: Auxílio à Pesquisa - Regular