Does chronic stimulation of both nicotinic and opioid receptors contribute to the loss of O2 and CO2 sensitivity in perinatal adrenomedullary chromaffin cells?
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abstract
Adaptation of the neonate to extrauterine life depends critically on catecholamine secretion (CAT) from adrenomedullary chromaffin cells (AMC). This CAT secretion is triggered by asphyxial stressors (e.g. hypoxia and hypercapnia) associated with the birthing process and these act directly on AMC, prior to functional splanchnic innervation. These sensing mechanisms are lost postnatally along a time course correlating roughly with innervation of AMC. Thus, the majority of juvenile AMC (>14 days) are unable to sense directly hypoxia and hypercapnia, although there is evidence that these properties may return following denervation. The splanchnic nerve releases various neurotransmitters including acetylcholine (ACh) which activate nicotinic ACh receptors (nAChR) and enkephalins which activate opioid receptors on AMC. Here, we test the hypothesis that activation of these receptors may initiate a signaling cascade leading to the loss of O2 and/or CO2 sensitivity. Recently, we showed that chronic stimulation of nAChR on AMC with nicotine, results in the loss of hypoxic, but not hypercapnic, sensitivity (Buttigieg et al. FASEB J 2007, in press). This loss of hypoxic sensitivity appears to be mediated by up‐regulation of KATP channels, which are activated by low PO2. Preliminary studies based on exposure of AMC to chronic opioid receptor stimulation suggest that this treatment leads to loss of both hypercapnic and hypoxic sensitivity. Thus, synaptic stimulation of opioid and nACh receptors on AMC may contribute to the normal developmental loss of O2 and CO2 sensitivity. Funded by: The Heart and Stroke Foundation (HSF) of Ontario. JB and SB were funded by a Focus on Stroke award from HSF of Canada.
