II. β-adrenergic receptors and catecholamine sensitive adenylate cyclase in the developing rat lung

Ontogeny of β-Adrenergic Receptors in the Rat Lung: Effects of Hypothyroidism

“…Betal-and P2-adrenergic receptor sites (80% P2:20% PI) were identified in the present study in both euthyroid and hypothyroid animals, in agreement with previous studies (16,26). Thus the thyroid hormone dependent increase in P-adrenergic receptors affects both PI-and &-adrenergic subtypes equally and the loss in receptor sites is not likely to be accounted for by a loss of a single cell type containing Padrenergic sites.…”

“…Cheng et al (5) have also recently demonstrated the role of corticosteroids on the prenatal increase in pulmonary /3-adrenergic receptors. In preliminary studies of the postnatal maturation of the /3-adrenergic receptor in rat lung, we noted that a thyroid dependent increase in P-adrenergic receptors occurred between postnatal days 14 and 28, during the period of increased thyroid gland activity and increased serum triiodothyronine (T3) and thyroxine (T4) concentrations which occurs late in neonatal life in this species as compared to the human (8,26,27). Several studies have also demonstrated that thyroid hormones or the thyroid analog 3,s-dimethyl-3'-isopropyl-1-thyronine (DIMIT) may enhance pulmonary maturation in the late fetal period in mammals (1,23,32).…”

“…These effects are presumably the result of the interactions of adrenergic agonists with P-adrenergic receptors present on the plasma membranes of various pulmonary cells, resulting in the stimulation of adenylate cyclase thus increasing intracellular 3',5' cyclic adenosine monophosphate (CAMP) (2,17). Studies from this laboratory have recently demonstrated that pulmonary /3-adrenergic receptors in the rat and rabbit increase dramatically during late gestation and during the suckling period, reaching adult levels by 28 days of postnatal age (26). Cheng et al (5) have also recently demonstrated the role of corticosteroids on the prenatal increase in pulmonary /3-adrenergic receptors.…”

“…Binding studies. Binding studies were performed in triplicate assays as previously described, in buffer containing 10 mM MgC12, 50 mM Tris-HC1 (pH 7.4) and 30-60 pg of lung membrane protein (26)(27)(28)(29). Specific binding at 5 nM (-)-[3H]DHA was also determined in frltered crude lung homogenates to estimate total receptor number per lung.…”

“…The statistical significance of differences in binding capacity or affinity among hypothyroid, T4-treated, and normal control rat lungs at each age were determined by a one way analysis of variance, corrected by the Neuman-Kuels test (22). To determine /3-adrenergic subtypes in rat lung (&)-['251]HYP binding was performed as previously described by Minneman et al (16) in an assay volume of 250 pliters containing 10-20 pg membrane protein and 100 pM GTP or Gpp(NH)p in a buffer containing 10 mM MgC12, 50 mM Tris-HC1 (pH 7.4) at 37OC after 30 min incubation (26,28). Nonspecific binding was identical whether determined in the presence of M (-)alprenolo1 or lo-" M (-)-isoproterenol and was less than 10% of total binding near the KD for (?)-['251]HYP.…”