title: Ontogeny of O2 and CO2//H+ chemosensitivity in adrenal chromaffin cells: role of innervation.
abstract: The adrenal medulla plays a key role in the physiological responses of developing and mature mammals by releasing catecholamines (CAT) during stress. In rodents and humans, the innervation of CAT-producing, adrenomedullary chromaffin cells (AMCs) is immature or absent during early postnatal life, when these cells possess 'direct' hypoxia- and CO2/H(+)-chemosensing mechanisms. During asphyxial stressors at birth, these mechanisms contribute to a CAT surge that is critical for adaptation to extra-uterine life. These direct chemosensing mechanisms regress postnatally, in parallel with maturation of splanchnic innervation. Here, we review the evidence that neurotransmitters released from the splanchnic nerve during innervation activate signaling cascades that ultimately cause regression of direct AMC chemosensitivity to hypoxia and hypercapnia. In particular, we consider the roles of cholinergic and opioid receptor signaling, given that splanchnic nerves release acetylcholine and opiate peptides onto their respective postsynaptic nicotinic and opioid receptors on AMCs. Recent in vivo and in vitro studies in the rat suggest that interactions involving α7 nicotinic acetylcholine receptors (nAChRs), the hypoxia inducible factor (HIF)-2α signaling pathway, protein kinases and ATP-sensitive K(+) (KATP) channels contribute to the selective suppression of hypoxic chemosensitivity. In contrast, interactions involving μ- and/or δ-opiod receptor signaling pathways contribute to the suppression of both hypoxic and hypercapnic chemosensitivity, via regulation of the expression of KATP channels and carbonic anhydrase (CA I and II), respectively. These data suggest that the ontogeny of O2 and CO2/H(+) chemosensitivity in chromaffin cells can be regulated by the tonic release of presynaptic neurotransmitters.
authors.affiliation: Department of Biology, McMaster University, Hamilton, ON, Canada, L8S 4K1.
authors.forename: Shaima
authors.initials: S
authors.lastname: Salman
authors.forename: Josef
authors.initials: J
authors.lastname: Buttigieg
authors.forename: Colin A
authors.initials: CA
authors.lastname: Nurse
mesh_terms: D000313:Adrenal Medulla / Q000196:embryology / Q000294:innervation* / Q000502:physiology*; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D015687:Cell Hypoxia; D019439:Chromaffin Cells / Q000502:physiology*; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D015398:Signal Transduction; D013153:Splanchnic Nerves / Q000196:embryology / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D002245:Carbon Dioxide; D010100:Oxygen
keywords: Adrenal chromaffin cells; Catecholamine secretion; HIF-2α; Hypercapnia; Hypoxia; KATP channels; Neonate; Nicotine; Opioids