Activation of central adenosine A(2A) receptors enhances superior laryngeal nerve stimulation-induced apnea in piglets via a GABAergic pathway.

Abstract

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.

• Authors: Jalal M Abu-Shaweesh
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 103 Issue 4 Pg. 1205-11 (Oct 2007) ISSN: 8750-7587 [Print] United States
• PMID: 17656623 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• GABA Antagonists
• Phenethylamines
• Receptor, Adenosine A2A
• 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
• gamma-Aminobutyric Acid
• Adenosine
• Bicuculline

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Animals
• Animals, Newborn
• Apnea (metabolism, physiopathology, prevention & control)
• Bicuculline (pharmacology)
• Blood Pressure (drug effects)
• Cisterna Magna
• Disease Models, Animal
• Drug Antagonism
• Electric Stimulation
• GABA Antagonists (pharmacology)
• Heart Rate (drug effects)
• Injections, Intraventricular
• Laryngeal Nerves (drug effects, metabolism, physiopathology)
• Phenethylamines (pharmacology)
• Phrenic Nerve (drug effects, physiology)
• Receptor, Adenosine A2A (drug effects, metabolism)
• Swine (physiology)
• gamma-Aminobutyric Acid (physiology)