Isolated rat fetal distal lung epithelial (FDLE) cells were cultured (˜48 h) on permeable supports in medium devoid of hormones and growth factors whilst PO2 was maintained at the level found in either the fetal (23 mmHg) or the postnatal (100 mmHg) alveolar regions. The cells became incorporated into epithelial layers that generated a basal short-circuit current (ISC) attributable to spontaneous Na+ absorption. Cells at neonatal PO2 generated larger currents than did cells at fetal PO2, indicating that this Na+ transport process is oxygen sensitive. Irrespective of PO2, isoprenaline failed to elicit a discernible change in ISC, demonstrating that ß-adrenoceptor agonists do not stimulate Na+ transport under these conditions. However, isoprenaline did elicit cAMP accumulation in these cells, indicating that functionally coupled ß-adrenoceptors are present. Further experiments showed that isoprenaline did increase ISC in cells treated (24 h) with a combination of tri-iodothyronine (T3, 10 nm) and dexamethasone (200 nm). Studies of basolaterally permeabilised cells showed that these hormones are essential for the isoprenaline-evoked increase in the apical membrane's Na+ conductance (GNa), whereas isoprenaline-evoked changes in apical Cl- conductance (GCl) can occur in both control and hormone-treated cells. Irrespective of their hormonal status, FDLE cells thus express ß-adrenoceptors that are functionally coupled to adenylate cyclase, and allow ß-adrenoceptor agonists to modulate the apical membrane's anion conductance. However, T3 and dexamethasone are needed if these receptors are to exert control over GNa. These hormones may thus play an important role in the functional maturation of the lung by allowing ß-adrenoceptor-mediated control over epithelial Na+ channels in the apical plasma membrane.
Ramminger, S. J., Inglis, S. K., Olver, R. E., & Wilson, S. M. (2002). Hormonal modulation of Na+ transport in rat fetal distal lung epithelial cells. Journal of Physiology, 544(2), 567-577. https://doi.org/10.1113/jphysiol.2002.022459