ABSTRACT. We designed experiments to determine whether P-adrenergic receptors are present and functional in human fetal lung during the 2nd trimester of gestation. To determine the presence of p receptors, characterize their binding sites, and assess changes in receptor with gestational age, we performed radioligand binding assays with the specific, high-affinity P antagonist, '251-iodocyanopindolol, in membrane particulates from the lungs of 2nd trimester abortuses (15-23 wk). Binding of '251-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 > epinephrine >> norepinephrine) were consistent with a predominance of 8-2 receptors; this predominance was confirmed by competition studies with the specific P-2 receptor antagonist ICI 118-551 (75% 8-2,25% P-1). The concentration of B-adrenergic receptors increased with gestational age. To assess the functional coupling of the fi receptors, we tested the ability of receptor occupancy to activate adenylate cyclase. For this assay, we incubated minced human fetal lung with P agonists and determined the amount of cAMP generated. P Agonists stimulated cAMP generation more than 2-fold. We conclude that Padrenergic receptors are present and functional in human fetal lung as early as the 2nd trimester. (Pediatr Res 21:142-147,1986) Abbreviations ICYP, '2~-iodocyanopindolol ATP, adenosine triphosphate CAMP, cyclic adenosine monophosphate Gpp(NH)p, 5'-guanylylimidodiphosphate GTP, guanosine triphosphate K,,, dissociation constant There is increasing evidence for an integral role of adrenergic responses in the complex transition which the fetal lungs undergo in preparation for extrauterine life. Indirect evidence comes from clinical situations in which infants are not exposed to high levels of the adrenergic catecholamines, epinephrine and norepinephrine. For example, infants born by cesarean section without labor Received March 26, 1986: accepted September 18, 1986 have lower concentrations of catecholamines in amniotic fluid and cord blood than do those delivered vaginally or by cesarean section after labor (I). In association with these lower catecholamine levels, infants born by cesarean section without labor have a higher incidence of breathing difficulties (2), less mature biochemical indices of lung maturity (3,4), and lower tidal volumes and lung compliance (1) than do other infants. In contrast, infants born to mothers who received P-adrenergic agonists immediately before delivery are reported to have a lower incidence of hyaline membrane disease (5).In other species, there is substantial experimental evidence that P-adrenergic responses are involved in fetal lung maturation (6). Administration of P-adrenergic agonists to fetal sheep and rabbits significantly decreases lung water content (7,8), increases surfactant release (9, lo), and increases lung stability (1 1, 12). In fetal rabbits,...