Transforming growth factor-alpha increases alveolar liquid clearance in anesthetized ventilated rats

Am J Physiol. 1996 Aug;271(2 Pt 1):L236-44. doi: 10.1152/ajplung.1996.271.2.L236.


The effect of transforming growth factor-alpha (TGF-alpha) on alveolar liquid clearance was examined in ventilated, anesthetized rats. An isosmolar Ringer lactate solution with 10, 50, or 200 ng/ml TGF-alpha and 125I-labeled albumin as the alveolar protein tracer was instilled into the right lower lung lobe; the rats were studied for 1 and 4 h. Compared with control rats, addition of 50 ng/ml TGF-alpha to the instilled fluid increased alveolar liquid clearance by 47% over 1 h and by 66% over 4 h (P < 0.05). This increase was similar to the 50% increase in alveolar liquid clearance over 1 h in rats instilled with a beta-adrenergic agonist, salmeterol (28). There was a dose-dependent effect of TGF-alpha (10, 50, 200 ng/ml) on alveolar liquid clearance. The combination of both TGF-alpha and salmeterol did not have an additive effect on alveolar liquid clearance. The TGF-alpha-stimulated increase in alveolar liquid clearance was inhibited by amiloride (10(-4) M), indicating that the increase in clearance depended on increased Na+ uptake across the alveolar epithelium. There was only a twofold increase in intracellular cAMP levels in isolated rat alveolar epithelial type II cells after stimulation with TGF-alpha. In contrast, beta-adrenergic agonist treatment increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels more than tenfold. Genistein (10(-6) M), a tyrosine protein kinase inhibitor, inhibited the TGF-alpha-stimulated increase in alveolar liquid clearance. In summary, TGF-alpha can stimulate in vivo alveolar liquid clearance at a rate similar to beta-adrenergic stimulation by increasing Na+ uptake by alveolar epithelial type II cells. However, the effect may be mediated by a non-cAMP dependent mechanism. Because genistein blocked the increase in alveolar fluid clearance, the signal transduction may involve genistein-dependent phosphorylation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Albuterol / analogs & derivatives
  • Albuterol / pharmacology
  • Amiloride / pharmacology
  • Animals
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Enzyme Inhibitors / pharmacology
  • Genistein
  • Isoflavones / pharmacology
  • Isotonic Solutions / pharmacokinetics
  • Male
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Ringer's Lactate
  • Salmeterol Xinafoate
  • Transforming Growth Factor alpha / pharmacology*


  • Adrenergic beta-Agonists
  • Enzyme Inhibitors
  • Isoflavones
  • Isotonic Solutions
  • Ringer's Lactate
  • Transforming Growth Factor alpha
  • Salmeterol Xinafoate
  • Amiloride
  • Genistein
  • Cyclic AMP
  • Protein-Tyrosine Kinases
  • Cyclic GMP
  • Albuterol