Sulfonylurea receptor expression in rat brain: effect of chronic hypoxia during development.
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.
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Department of Pediatrics (Section of Respiratory Medicine, Laboratory of Respiratory Neurobiology), Yale University School of Medicine, New Haven, Connecticut 06510.
Eisenman
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Haddad
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D018528:ATP-Binding Cassette Transporters; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism / Q000473:pathology; D005905:Glyburide / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism*; D064233:Sulfonylurea Receptors; D014018:Tissue Distribution
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D005905:Glyburide