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Dibutyryl cAMP induces a gestation-dependent absorption of fetal lung liquid
D V Walters1, C A Ramsden, R E Olver
1Paediatric Department, University College London, United Kingdom.
Insights
The fetal lamb lung
Area of Science:
- Fetal Physiology
- Pulmonary Medicine
- Cellular Signaling
Background:
- Fetal lung liquid secretion is crucial for lung development.
- The adenosine 3',5'-cyclic monophosphate (cAMP) pathway regulates this secretion.
- Understanding the maturation of this pathway is key to fetal lung health.
Purpose of the Study:
- To investigate the gestational maturation of the cAMP-dependent pathway controlling fetal lung liquid secretion.
- To determine how dibutyryl cAMP (DBcAMP) affects fetal lung liquid secretion at different gestational ages.
Main Methods:
- Experiments involved chronically catheterized fetal lambs aged 123-141 days.
- Fetal lungs were exposed to dibutyryl cAMP (DBcAMP).
- The effects of DBcAMP on lung liquid volume flow were measured and compared across gestational ages, with and without amiloride.
Main Results:
- DBcAMP's effect on fetal lung liquid secretion was significantly dependent on gestational age.
- Immature fetuses showed slowed secretion, while mature fetuses exhibited absorption.
- Amiloride blocked DBcAMP-induced changes, indicating involvement of sodium (Na+) transport.
Conclusions:
- DBcAMP stimulates a change in lung liquid secretion via increased apical membrane Na+ permeability, similar to epinephrine.
- The maturation of this cAMP-dependent pathway is limited by factors downstream of intracellular cAMP generation.
Abstract:
The maturation of the adenosine 3',5'-cyclic monophosphate-(cAMP) dependent pathway controlling fetal lung liquid secretion was examined in experiments in which the lungs of chronically catheterized fetal lambs (123-141 days gestational age) were exposed to dibutyryl cAMP (DBcAMP, 10(-4) M). The effect of DBcAMP was markedly gestation dependent, with the greatest effect observed in the most mature fetuses. In immature fetuses (less than 130 days, mean age 125 days) DBcAMP caused slowing of secretion, with maximal effect at 5 h. With increasing maturity the effect of DBcAMP was more pronounced and occurred earlier so that in mature fetuses (mean age 140 days) lung liquid absorption took place, with maximal effect at 2 h. Changes in lung liquid volume flow induced by DBcAMP could be blocked by addition of 10(-4) M amiloride to lung liquid. It is concluded that 1) DBcAMP induces a change in lung liquid secretion that, like epinephrine, is mediated via an increase in Na+ permeability of the apical membrane of the lung epithelium and 2) the rate-limiting step in the maturation of this process must lie beyond the generation of intracellular cAMP.