CHARACTERIZATION OF THE BETA-ADRENERGIC-RECEPTOR IN ISOLATED HUMAN FETAL LUNG TYPE-II CELLS

Functioning of the beta-adrenergic response system is important for successful transition of the neonate from fetal life to breathing air. We characterized the beta-adrenergic receptors on human fetal lung type II cells, the cell type responsible for many pulmonary responses sensitive to beta-adrenergic stimulation. Type II cells were isolated from human fetal lung explants, and membrane particulates prepared from these cells were used for radioligand binding studies. I-125-iodocyanopindolol, a specific beta-adrenergic antagonist, bound to a single class of saturable, high-affinity binding sites on type II cell membranes with a receptor concentration of 78 +/- 9 fmol receptor/mg membrane protein, a k(d) of 79 +/- 18 nM, and 958 +/- 120 receptors per cell. Binding was stereoselective with l-propranolol binding with higher affinity than the inactive d-isomer. The binding site had the characteristics of a beta-2-adrenergic receptor. The order of potency of beta-adrenergic agonists was isoproterenol > epinephrine >> norepinephrine. The beta-2-selective antagonist ICI 118 551 competed for a single class of high-affinity sites. Agonist binding affinity was reduced in the presence of guanyl nucleotides, consistent with receptors coupled to guanine nucleotide binding proteins. beta-Adrenergic agonists also stimulated adenylyl cyclase in these membrane preparations. I-125-iodocyanopindolol binding to membranes prepared from human fetal lung fibroblasts indicated fewer receptors (404 +/- 68) than were present on type II cells. Work by others has suggested a difference in lung function and lung-beta-adrenergic receptor concentration between males and females. After culturing midgestation human fetal lung for 5 d we found no significant difference between the beta-adrenergic receptor number per type II cell for male (820 +/- 165) and female (1107 +/- 220) specimens.