alpha 4-Containing nicotinic receptors contribute to the effects of perinatal nicotine on ventilatory and metabolic responses of neonatal mice to ambient cooling

作者：Avraam Joanne^*; Cummings Kevin J; Frappell Peter B

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2016, 311(4): R727-R734.

DOI：10.1152/ajpregu.00247.2016

• breathing
• neonate
• nicotine
• nicotinic receptor
• thermogenesis

Among numerous studies, perinatal nicotine exposure (PN) has had variable effects on respiratory control in the neonatal period. The effects of acute nicotine exposure on breathing are largely mediated by alpha 4-containing nicotine acetylcholine receptors (nAChRs). These receptors are also involved in thermoregulatory responses induced by both acetylcholine and nicotine. We therefore hypothesized that alpha 4-containing nAChRs would mediate the effects of PN on the metabolic and ventilatory responses of neonates to modest cold exposure. Wild-type (WT) and alpha 4 knockout (KO) mice were exposed to 6 mg.kg(-1).day(-1) nicotine or vehicle from embryonic day 14. At postnatal day (P) 7 mice were cooled from an ambient temperature (T-A) of 32 to 20 degrees C. Body temperature (T-B), rate of O-2 consumption (VO2), ventilation (V-E), respiratory frequency (F-B), and tidal volume (V-T) were continually monitored. An absence of alpha 4 had no effect on the metabolic response to ambient cooling. Surprisingly, PN selectively increased the metabolic response of KO pups to cooling. Regardless, KO pups became hypothermic to the same degree as WT pups, and for both genotypes the drop in TB was exacerbated by PN. PN led to hyperventilation in WT pups caused by an increase in V-T, an effect that was absent in alpha 4 KO littermates. We show that PN interacts with alpha 4-containing nAChRs in unique ways to modulate the control of breathing and thermoregulation in the early postnatal period.

• 出版日期2016-10-1