Xia Y, Eisenman D, Haddad G G
Department of Pediatrics (Section of Respiratory Medicine, Laboratory of Respiratory Neurobiology), Yale University School of Medicine, New Haven, Connecticut 06510.
Pediatr Res. 1993 Nov;34(5):634-41. doi: 10.1203/00006450-199311000-00015.
Sulfonylurea receptors are believed to be related to ATP-sensitive potassium channels and play a key role during hypoxia/ischemia in the CNS. Our previous work has shown that these receptors in rat brainstem neurons are more important in the adult rat than in the newborn during hypoxia. In the present study, we studied the time course of postnatal development of sulfonylurea receptors in detail and the effect of chronic hypoxia on receptor density in newborn pups and adult rats exposed to hypoxia either as fetuses or as 90-d-old rats using receptor binding and autoradiography. Our current results show that sulfonylurea receptor density 1) was very low at birth and developed fast within the first 2 postnatal wk and then gradually reached adult levels and 2) continued to increase in the cortex and cerebellum but decreased in the brainstem with little or no change in other areas after postnatal wk 5. Chronic hypoxia 1) decreased body weight, brain size, and brain protein concentration and 2) increased sulfonylurea receptor density in utero but had much less of an effect in the adult. From these data, we conclude that sulfonylurea receptors develop mostly in the first 2 wk postnatally and chronic hypoxia increases sulfonylurea receptor expression in utero in spite of the fact that overall protein decreases.
磺脲类受体被认为与ATP敏感性钾通道有关，并且在中枢神经系统的缺氧/缺血过程中起关键作用。我们之前的研究表明，在缺氧状态下，大鼠脑干神经元中的这些受体在成年大鼠中比在新生大鼠中更为重要。在本研究中，我们使用受体结合和放射自显影技术，详细研究了磺脲类受体出生后发育的时间进程，以及慢性缺氧对新生幼崽和成年大鼠（无论是胎儿期还是90日龄大鼠）暴露于缺氧环境下受体密度的影响。我们目前的结果显示，磺脲类受体密度1）在出生时非常低，在出生后的前2周内迅速发育，然后逐渐达到成年水平；2）在出生后第5周后，皮质和小脑中的受体密度持续增加，而脑干中的受体密度降低，其他区域几乎没有变化。慢性缺氧1）降低了体重、脑大小和脑蛋白浓度；2）在子宫内增加了磺脲类受体密度，但对成年大鼠的影响要小得多。从这些数据中，我们得出结论，磺脲类受体主要在出生后的前2周发育，并且尽管总体蛋白减少，但慢性缺氧会增加子宫内磺脲类受体的表达。
