Regulation of beta-adrenergic receptor-mediated processes in fetal rat lung: selective desensitization caused by chronic terbutaline exposure.
Fetal lung beta-receptors become effectively coupled to lung fluid reabsorption and enzymes involved in surfactant synthesis on the day before birth, a period when circulating catecholamine levels are high. Accordingly, we examined the effects of repeated maternal terbutaline exposure on beta-receptor binding capabilities and beta-receptor-mediated processes in the fetal rat lung. Administration of terbutaline to pregnant rats on gestational day 17-20 produced significant reductions in beta-receptor binding to membrane preparations. Similarly, beta-receptor-mediated stimulation of adenylate cyclase activity and ornithine decarboxylase activity showed marked desensitization in the terbutaline-exposed fetuses. However, the linkage of beta-receptors to lung fluid reabsorption and phosphatidic acid phosphatase, an enzyme involved in surfactant synthesis, did not desensitize with chronic terbutaline pretreatment; both of these processes displayed the normal onset of responsiveness on gestational day 21 in the treated animals, as well as a normal magnitude of response. Hence, beta-receptor-mediated events in the developing lung may be differentially regulated during exposure to agonists, allowing the selective expression or depression of function when circulating catecholamine levels are high.
Kudlacz
E M
EM
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Navarro
H A
HA
Slotkin
T A
TA
D000042:Absorption / Q000187:drug effects; D000262:Adenylyl Cyclases / Q000032:analysis; D000367:Age Factors; D000818:Animals; D005260:Female; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000032:analysis; D010711:Phosphatidate Phosphatase / Q000032:analysis; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013726:Terbutaline / Q000633:toxicity*
D011943:Receptors, Adrenergic, beta; D010711:Phosphatidate Phosphatase; D009955:Ornithine Decarboxylase; D000262:Adenylyl Cyclases; D013726:Terbutaline