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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Falquetto, Barbara [1] ; Oliveira, Luiz M. [1] ; Takakura, Ana C. [1] ; Mulkey, Daniel K. [2] ; Moreira, Thiago S. [3]
Total Authors: 5
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Neuropharmacology; v. 138, p. 47-56, AUG 2018.
Web of Science Citations: 3
Abstract

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)

FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
Grantee:Thiago dos Santos Moreira
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 16/23281-3 - Encephalic regions responsible for neuroplasticity observed in respiratory response induced by hypercapnia in a modelo of Parkinson's Disease
Grantee:Ana Carolina Takakura Moreira
Support Opportunities: Regular Research Grants
FAPESP's process: 16/22069-0 - Amelioration of the brainstem vascular imbalances in an spontaneously hypertensive rats with exercise
Grantee:Thiago dos Santos Moreira
Support Opportunities: Regular Research Grants