Czapla M A, Simakajornboon N, Holt G A, Gozal D
Department of Pediatrics, Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
J Appl Physiol (1985). 1999 Jul;87(1):363-9. doi: 10.1152/jappl.1999.87.1.363.
Tyrosine kinases (TKs) exert multiple regulatory roles in neuronal activity and synaptic plasticity and could be involved in modulation of cardiovascular and respiratory control mechanisms within the dorsocaudal brain stem. To study this issue, the cardioventilatory responses to 1-microl microinjection within the dorsocaudal brain stem of either vehicle (Veh), the inactive TK inhibitor analog tyrphostin A1 (A1; 1 mM), or the active TK inhibitors genistein (Gen; 10 mM) and tyrphostin A25 (A25; 1 mM) were assessed by whole body plethysmography in unrestrained Sprague-Dawley adult rats. No changes in minute ventilation, heart rate, or mean arterial pressure occurred with Veh, A1, Gen, or A25 during room air breathing (P not significant). However, Gen and A25 attenuated the peak hypoxic ventilatory responses (HVR) to 10% O(2) (P < 0.006 vs. Veh), whereas A1 did not modify HVR (P not significant). HVR reductions by Gen and A25 were primarily due to diminished respiratory frequency enhancements (P < 0.002). No changes in heart rate or mean arterial pressure responses occurred during hypoxia with TK inhibition. In addition, increases in tyrosine phosphorylation of the NR2A/B subunits, but not of the NR2C subunit, of the N-methyl-D-aspartate receptor occurred at 5, 30, and 60 min of hypoxia in the dorsocaudal brain stem and returned to baseline values at 120 min. We conclude that hypoxia induces tyrosine phosphorylation of the N-methyl-D-aspartate glutamate receptor, and TK inhibition within the dorsocaudal brain stem attenuates components of HVR in conscious rats.
酪氨酸激酶（TKs）在神经元活动和突触可塑性中发挥多种调节作用，并可能参与背尾脑干内心血管和呼吸控制机制的调节。为研究此问题，通过全身体积描记法在未束缚的成年Sprague-Dawley大鼠中评估了对背尾脑干内注射1微升载体（Veh）、非活性TK抑制剂类似物 tyrphostin A1（A1；1 mM）或活性TK抑制剂染料木黄酮（Gen；10 mM）和tyrphostin A25（A25；1 mM）的心肺反应。在室内空气呼吸期间，Veh、A1、Gen或A25对分钟通气量、心率或平均动脉压均无影响（P无显著性差异）。然而，Gen和A25减弱了对10% O₂ 的峰值低氧通气反应（HVR）（与Veh相比，P < 0.006），而A1未改变HVR（P无显著性差异）。Gen和A25导致的HVR降低主要是由于呼吸频率增强减弱（P < 0.002）。在低氧期间，TK抑制对心率或平均动脉压反应无影响。此外，在背尾脑干低氧5、30和60分钟时，N-甲基-D-天冬氨酸受体的NR2A/B亚基而非NR2C亚基的酪氨酸磷酸化增加，并在120分钟时恢复到基线值。我们得出结论，低氧诱导N-甲基-D-天冬氨酸谷氨酸受体的酪氨酸磷酸化，并且背尾脑干内的TK抑制减弱了清醒大鼠HVR的组成部分。
