β-Adrenergic Receptors and cAMP Response Increase during Explant Culture of Human Fetal Lung: Partial Inhibition by Dexamethasone

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Abstract

ABSTRACT: 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 2-fold. 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.

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Correspondence to James M Roberts.

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