BETA-ADRENERGIC RECEPTORS AND CAMP RESPONSE INCREASE DURING EXPLANT CULTURE OF HUMAN FETAL LUNG - PARTIAL INHIBITION BY DEXAMETHASONE

被引:11
作者
DAVIS, DJ
JACOBS, MM
BALLARD, PL
GONZALES, LK
ROBERTS, JM
机构
[1] UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,HSE 1462,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143
[3] UNIV CALIF SAN FRANCISCO,DEPT OBSTET GYNECOL & REPROD SCI,SAN FRANCISCO,CA 94143
关键词
D O I
10.1203/00006450-199009000-00003
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
We studied β-adrenergic receptors and responses in human fetal lung (15-25 wk gestation) maintained in explant culture with and without added dexamethasone. To determine β-adrenergic receptor concentration, we performed radioligand binding assays with [125I]-iodocyanopindolol. We also examined the ability of isoproterenol to stimulate cAMP generation as a measure of response to β-adrenergic receptor occupancy. In control cultures, β-receptor concentration increased significantly from d 0 to 3 of culture and thereafter remained stable. The kd (−24 pM) of [125I]-iodocyanopindolol did not change with time in culture. The ability of isoproterenol to stimulate cAMP generation over basal levels increased in controls throughout the 5 d in explant culture. Addition of dexamethasone (10 nM) to the culture medium partially blocked the increase in β-receptor concentration and decreased both cAMP content and generation (basal and stimulated) in a dose-dependent manner (median effective concentration −1 nM). In these same explants, dexamethasone increased the activity of fatty acid synthetase, an enzyme important in surfactant synthesis, more than 2fold. Our results indicate that β-adrenergic receptors and isoproterenol stimulation of cAMP generation increase spontaneously in human fetal lung grown in explant culture. Dexamethasone, which accelerates other aspects of human lung development in vitro, decreases β-adrenergic receptor concentration and inhibits β-adrenergic responses. © 1990 International Pediatric Research Foundation, Inc.
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页码:190 / 195
页数:6
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