Alea O A, Czapla M A, Lasky J A, Simakajornboon N, Gozal E, Gozal D
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Am J Physiol Regul Integr Comp Physiol. 2000 Nov;279(5):R1625-33. doi: 10.1152/ajpregu.2000.279.5.R1625.
Activation of platelet-derived growth factor-beta (PDGF-beta) receptors in the nucleus of the solitary tract (nTS) modulates the late phase of the acute hypoxic ventilatory response (HVR) in the rat. We hypothesized that temporal changes in PDGF-beta receptor expression could underlie the ventilatory acclimatization to hypoxia (VAH). Normoxic ventilation was examined in adult Sprague-Dawley rats chronically exposed to 10% O(2), and at 0, 1, 2, 7, and 14 days, Northern and Western blots of the dorsocaudal brain stem were performed for assessment of PDGF-beta receptor expression. Although no significant changes in PDGF-beta receptor mRNA occurred over time, marked attenuation of PDGF-beta receptor protein became apparent after day 7 of hypoxic exposure. Such changes were significantly correlated with concomitant increases in normoxic ventilation, i.e., with VAH (r: -0.56, P < 0.005). In addition, long-term administration of PDGF-BB in the nTS via osmotic pumps loaded with either PDGF-BB (n = 8) or vehicle (Veh; n = 8) showed that although no significant changes in the magnitude of acute HVR occurred in Veh over time, the typical attenuation of HVR by PDGF-BB decreased over time. Furthermore, PDGF-BB microinjections did not attenuate HVR in acclimatized rats at 7 and 14 days of hypoxia (n = 10). We conclude that decreased expression of PDGF-beta receptors in the dorsocaudal brain stem correlates with the magnitude of VAH. We speculate that the decreased expression of PDGF-beta receptors is mediated via internalization and degradation of the receptor rather than by transcriptional regulation.
孤束核（nTS）中血小板源性生长因子-β（PDGF-β）受体的激活可调节大鼠急性低氧通气反应（HVR）的晚期阶段。我们推测，PDGF-β受体表达的时间变化可能是低氧通气习服（VAH）的基础。对长期暴露于10%氧气的成年Sprague-Dawley大鼠进行常氧通气检测，并在0、1、2、7和14天时，对脑桥尾端背侧脑干进行Northern和Western印迹分析，以评估PDGF-β受体的表达。尽管随着时间的推移，PDGF-β受体mRNA没有显著变化，但在低氧暴露7天后，PDGF-β受体蛋白明显衰减。这些变化与常氧通气的同时增加显著相关，即与VAH相关（r：-0.56，P<0.005）。此外，通过装有PDGF-BB（n = 8）或载体（Veh；n = 8）的渗透泵在nTS中长期给予PDGF-BB，结果显示，尽管Veh组急性HVR的幅度随时间没有显著变化，但PDGF-BB对HVR的典型衰减随时间而降低。此外，在低氧7天和14天时，对习服大鼠进行PDGF-BB微量注射并不会减弱HVR（n = 10）。我们得出结论，脑桥尾端背侧脑干中PDGF-β受体表达的降低与VAH的幅度相关。我们推测，PDGF-β受体表达的降低是通过受体内化和降解介导的，而不是通过转录调控。
