4.7 Article

Neonatal intermittent hypoxia impairs neuronal nicotinic receptor expression and function in adrenal chromaffin cells

期刊

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 299, 期 2, 页码 C381-C388

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00530.2009

关键词

adrenal medullary chromaffin cells; nicotinic cholinergic receptors; recurrent apneas; reactive oxygen species; catecholamine secretion

资金

  1. National Institutes of Health [HL-76537, HL-90554, HL-86493, HL-089616, GM-081809]
  2. Philip Morris International

向作者/读者索取更多资源

Souvannakitti D, Kuri B, Yuan G, Pawar A, Kumar GK, Smith C, Fox AP, Prabhakar NR. Neonatal intermittent hypoxia impairs neuronal nicotinic receptor expression and function in adrenal chromaffin cells. Am J Physiol Cell Physiol 299: C381-C388, 2010. First published May 12, 2010; doi: 10.1152/ajpcell.00530.2009.-We recently reported that adrenomedullary chromaffin cells (AMC) from neonatal rats treated with intermittent hypoxia (IH) exhibit enhanced catecholamine secretion by hypoxia (Souvannakitti D, Kumar GK, Fox A, Prabhakar NR. J Neurophysiol 101: 2837-2846, 2009). In the present study, we examined whether neonatal IH also facilitate AMC responses to nicotine, a potent stimulus to chromaffin cells. Experiments were performed on rats exposed to either IH (15-s hypoxia-5min normoxia; 8 h/day) or to room air (normoxia; controls) from ages postnatal day 0 (P0) to P5. Quantitative RT-PCR analysis revealed expression of mRNAs encoding alpha(3)-, alpha(5)-, alpha(7)-, and beta(2)-and beta(4)-nicotinic acetylcholine receptor (nAChR) subunits in adrenal medullae from control P5 rats. Nicotine-elevated intracellular Ca2+ concentration ([Ca2+](i)) in AMC and nAChR antagonists prevented this response, suggesting that nAChRs are functional in neonatal AMC. In IH-treated rats, nAChR mRNAs were downregulated in AMC, which resulted in a markedly attenuated nicotine-evoked elevation in [Ca2+](i) and subsequent catecholamine secretion. Systemic administration of antioxidant prevented IH-evoked downregulation of nAChR expression and function. P35 rats treated with neonatal IH exhibited reduced nAChR mRNA expression in adrenal medullae, attenuated AMC responses to nicotine, and impaired neurogenic catecholamine secretion. Thus the response to neonatal IH lasts for at least 30 days. These observations demonstrate that neonatal IH downregulates nAChR expression and function in AMC via reactive oxygen species signaling, and the effects of neonatal IH persist at least into juvenile life, leading to impaired neurogenic catecholamine secretion from AMC.

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