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, EM; Navarro, HA; Slotkin, TA
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