Adenosine A2A receptors mediate GABAergic inhibition of respiration in immature rats
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Updated: Aug 16, 2026

Electrophysiology on Isolated Brainstem-spinal Cord Preparations from Newborn Rodents Allows Neural Respiratory Network Output Recording
Published on: November 19, 2015
Catherine A Mayer1, Musa A Haxhiu, Richard J Martin
1Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA. caa4@po.cwru.edu
Abstract:
Adenosine is a known inhibitor of respiratory output during early life. In this study we investigated the developmental changes in adenosine A2A-receptor activation on respiratory timing, as well as the relationship between adenosine and GABA. The specific adenosine A2A-receptor agonist CGS-21680 (CGS) or vehicle control was injected into the fourth ventricle of 14-day (n = 9), 21-day (n = 9), and adult (n = 5) urethane-anesthetized rats while diaphragm electromyogram was monitored as an index of respiratory neural output. CGS injection resulted in a decrease in frequency and/or apnea in all 14-day-old rats and in 66% of 21-day-old rats. There was no effect of CGS injection on respiratory timing in adult rats. Prior injection of the GABA(A)-receptor blocker bicuculline at 14 and 21 days eliminated the CGS-induced decrease in frequency and apnea. We conclude from these studies that the inhibitory effect of A2A-receptor activation on respiratory drive is age dependent and is mediated via GABAergic inputs to the inspiratory timing neural circuitry. These findings demonstrate an important mechanism by which xanthine therapy alleviates apnea of prematurity.
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