HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 103/4/1205    most recent 01420.2006v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Abu-Shaweesh, J. M. Search for Related Content PubMed PubMed Citation Articles by Abu-Shaweesh, J. M.

Activation of central adenosine A_2A receptors enhances superior laryngeal nerve stimulation-induced apnea in piglets via a GABAergic pathway

Department of Pediatrics, Case Medical Center and Case Western Reserve University, Cleveland, Ohio

Submitted 14 December 2006 ; accepted in final form 13 July 2007

Activation of the laryngeal mucosa results in apnea that is mediated through, and can be elicited via electrical stimulation of, the superior laryngeal nerve (SLN). This potent inhibitory reflex has been suggested to play a role in the pathogenesis of apnea of prematurity and sudden infant death syndrome, and it is attenuated by theophylline and blockade of GABA_A receptors. However, the interaction between GABA and adenosine in the production of SLN stimulation-induced apnea has not been previously examined. We hypothesized that activation of adenosine A_2A receptors will enhance apnea induced by SLN stimulation while subsequent blockade of GABA_A receptors will reverse the effect of A_2A receptor activation. The phrenic nerve responses to increasing levels of SLN stimulation were measured before and after sequential intracisternal administration of the adenosine A_2A receptor agonist CGS (n = 10) and GABA_A receptor blocker bicuculline (n = 7) in ventilated, vagotomized, decerebrate, and paralyzed newborn piglets. Increasing levels of SLN stimulation caused progressive inhibition of phrenic activity and lead to apnea during higher levels of stimulation. CGS caused inhibition of baseline phrenic activity, hypotension, and enhancement of apnea induced by SLN stimulation. Subsequent bicuculline administration reversed the effects of CGS and prevented the production of apnea compared with control at higher SLN stimulation levels. We conclude that activation of adenosine A_2A receptors enhances SLN stimulation-induced apnea probably via a GABAergic pathway. We speculate that SLN stimulation causes endogenous release of adenosine that activates A_2A receptors on GABAergic neurons, resulting in the release of GABA at inspiratory neurons and subsequent respiratory inhibition.

control of breathing; sudden infant death syndrome hypotension