Beta-adrenergic receptors and cyclic adenosine monophosphate generation in human fetal lung

We designed experiments to determine whether beta-adrenergic receptors are present and functional in human fetal lung during the 2nd trimester of gestation. To determine the presence of beta receptors, characterize their binding sites, and assess changes in receptor with gestational age, we performed radioligand binding assays with the specific, high-affinity beta antagonist, 125I-iodocyanopindolol, in membrane particulates from the lungs of 2nd trimester abortuses (15-23 wk). Binding of 125I-iodocyanopindolol was saturable and of high affinity (dissociation constant = 40 pM). Binding was stereoselective as determined by competition studies with (-) and (+) stereoisomers of propranolol. Agonist affinities (isoproterenol greater than epinephrine much greater than norepinephrine) were consistent with a predominance of beta-2 receptors; this predominance was confirmed by competition studies with the specific beta-2 receptor antagonist ICI 118-551 (75% beta-2, 25% beta-1). The concentration of beta-adrenergic receptors increased with gestational age. To assess the functional coupling of the beta receptors, we tested the ability of receptor occupancy to activate adenylate cyclase. For this assay, we incubated minced human fetal lung with beta agonists and determined the amount of cAMP generated. beta Agonists stimulated cAMP generation more than 2-fold. We conclude that beta-adrenergic receptors are present and functional in human fetal lung as early as the 2nd trimester.