Journal of Applied Physiology AJP: Renal Physiology
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J Appl Physiol (September 1, 2005). doi:10.1152/japplphysiol.00459.2005
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Submitted on April 22, 2005
Accepted on August 29, 2005

Adenosine A2A Receptors Mediate GABAergic Inhibition of Respiration in Immature Rats

Catherine A Mayer1*, Musa A Haxhiu2, Richard J Martin1, and Christopher G Wilson1

1 Department of Pediatrics, Rainbow Babies and Childrens Hospital and Case Western Reserve University, Cleveland, OH, USA
2 Department of Pediatrics, Rainbow Babies and Childrens Hospital and Case Western Reserve University, Cleveland, OH, USA; Department of Physiology and Biophysics, Howard University, Washington D.C., USA

* To whom correspondence should be addressed. E-mail: caa4{at}po.cwru.edu.

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 CGS21680 (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 monitoring diaphragm EMG 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 GABAA 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 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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