AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 2 187-L191, Copyright © 1994 by American Physiological Society

ARTICLES

TGF-beta 1 modulates beta-adrenergic receptor number and function in cultured human tracheal smooth muscle cells

M. Nogami, D. J. Romberger, S. I. Rennard and M. L. Toews
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198.

Pretreatment of cultured human tracheal smooth muscle cells with transforming growth factor-beta 1 (TGF-beta 1) decreased adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by intact cells stimulated with the beta-adrenergic agonist isoproterenol. The maximal inhibition of isoproterenol-stimulated cAMP accumulation by TGF-beta 1 was 31 +/- 3%, and the mean effective concentration (EC50) of TGF-beta 1 was approximately 1.5 pM. TGF-beta 1 decreased the maximal response to isoproterenol but did not change the EC50 value of isoproterenol. TGF-beta 1 did not change cAMP accumulation stimulated by forskolin. TGF-beta 1 pretreatment decreased isoproterenol-stimulated adenylyl cyclase activity measured in broken cell preparations, but did not change the fluoride-stimulated adenylyl cyclase activity. Together these results suggest that the TGF-beta 1 effect is not by direct inhibition of adenylyl cyclase or by decreased activity of the stimulatory GTP-binding protein. Saturation binding experiments with the beta-adrenergic receptor radioligand [125I]iodopindolol showed that TGF-beta 1 pretreatment decreased the beta-adrenergic receptor number. The protein synthesis inhibitor cycloheximide abolished the effect of TGF-beta 1 on both cAMP accumulation and on beta-adrenergic receptor number, indicating that protein synthesis is involved. These results suggest that TGF-beta 1 in the lung could play a role in changing the responsiveness of airway smooth muscle cells to endogenous catecholamines and to beta-adrenergic agonists used in therapy.

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