β-Adrenergic Receptors and Cyclic Adenosine Monophosphate Generation in Human Fetal Lung

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Abstract
We designed experiments to determine whether β-adrenergic receptors are present and functional in human fetal lung during the 2nd trimester of gestation. To determine the presence of β receptors, characterize their binding sites, and assess changes in receptor with gestational age, we performed radioligand binding assays with the specific, high-affinity β antagonist,I25I-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 stereo selective as determined by competition studies with (—) and (+) stereoisomers of propranolol. Agonist affinities (isoproterenol > epinephrine » norepinephrine) were consistent with a predominance of 0-2 receptors; this predominance was confirmed by competition studies with the specific β-2 receptor antagonist ICI 118-551 (75% β-2, 25% β-1). The concentration of β-adrenergic receptors increased with gestational age. To assess the functional coupling of the β receptors, we tested the ability of receptor occupancy to activate adenylate cyclase. For this assay, we incubated minced human fetal lung with β agonists and determined the amount of cAMP generated. β Agonists stimulated cAMP generation more than 2-fold. We conclude that β- adrenergic receptors are present and functional in human fetal lung as early as the 2nd trimester.