The in vivo respiratory phenotype of the adenosine A(1) receptor knockout mouse

Heitzmann, Dirk and Buehler, Philipp and Schweda, Frank and Georgieff, Michael and Warth, Richard and Thomas, Joerg (2016) The in vivo respiratory phenotype of the adenosine A(1) receptor knockout mouse. RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 222. pp. 16-28. ISSN 1569-9048, 1878-1519

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Abstract

The nucleoside adenosine has been implicated in the regulation of respiration, especially during hypoxia in the newborn. In this study the role of adenosine A(1) receptors for the control of respiration was investigated in vivo. To this end, respiration of unrestrained adult and neonatal adenosine A1 receptor knockout mice (A(1)R(-/-)) was measured in a plethysmographic device. Under control conditions (21% O-2) and mild hypoxia (12-15% O-2) no difference of respiratory parameters was observed between adult wildtype (A(1)R(+/+)) and A(1)R(-/-) mice. Under more severe hypoxia (6-10% O-2) A(1)R(+/+) mice showed, after a transient increase of respiration, a decrease of respiration frequency (f(R)) and tidal volume (V-T) leading to a decrease of minute volume (MV). This depression of respiration during severe hypoxia was absent in A(1)R(-/-) mice which displayed a stimulated respiration as indicated by the enhancement of MV by some 50-60%. During hypercapnia-hyperoxia (3-10% CO2/97-90 % O-2), no obvious differences in respiration of A(1)R(-/-) and A(1)R(+/+) was observed. In neonatal mice, the respiratory response to hypoxia was surprisingly similar in both genotypes. However, neonatal A(1)R(-/-) mice appeared to have more frequently periods of apnea during hypoxia and in the post-hypoxic control period. In conclusion, these data indicate that the adenosine A(1) receptor is an important molecular component mediating hypoxic depression in adult mice and it appears to stabilize respiration of neonatal mice. (C) 2015 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: HYPOXIC VENTILATORY RESPONSE; FETAL BREATHING MOVEMENTS; VENTRAL MEDULLARY SURFACE; RAT BRAIN-STEM; SYSTEMIC HYPOXIA; RETROTRAPEZOID NUCLEUS; CAROTID-BODY; ADULT RATS; CARDIOVASCULAR-RESPONSE; NEONATAL CAFFEINE; Adenosine; A(1) receptor knockout; Mouse; Hypoxia; HRD
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth
Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Mar 2019 11:16
Last Modified: 14 Mar 2019 11:17
URI: https://pred.uni-regensburg.de/id/eprint/2503

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