45 Citations (Scopus)

Abstract

Pretreatment of cultured human tracheal smooth muscle cells with transforming growth factor-β1 (TGF-β1) decreased adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by intact cells stimulated with the β- adrenergic agonist isoproterenol. The maximal inhibition of isoproterenol- stimulated cAMP accumulation by TGF-β1 was 31 ± 3%, and the mean effective concentration (EC 50 ) of TGF-β1 was ~1.5 pM. TGF-β1 decreased the maximal response to isoproterenol but did not change the EC 50 value of isoproterenol. TGF-β1 did not change cAMP accumulation stimulated by forskolin. TGF-β1 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-β1 effect is not by direct inhibition of adenylyl cyclase or by decreased activity of the stimulatory GTP-binding protein. Saturation binding experiments with the β-adrenergic receptor radioligand [ 125 I]iodopindolol showed that TGF-β1 pretreatment decreased the β-adrenergic receptor number. The protein synthesis inhibitor cycloheximide abolished the effect of TGF- β1 on both cAMP accumulation and on β-adrenergic receptor number, indicating that protein synthesis is involved. These results suggest that TGF-β1 in the lung could play a role in changing the responsiveness of airway smooth muscle cells to endogenous catecholamines and to β-adrenergic agonists used in therapy.

Original languageEnglish (US)
Pages (from-to)L187-L191
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume266
Issue number2 10-2
StatePublished - Jan 1 1994

Fingerprint

Transforming Growth Factors
Adrenergic Receptors
Smooth Muscle Myocytes
Isoproterenol
Adenylyl Cyclases
Adrenergic Agonists
Protein Synthesis Inhibitors
Colforsin
Cycloheximide
Fluorides
GTP-Binding Proteins
Cyclic AMP
Catecholamines
Lung

Keywords

  • adenosine 3',5'-cyclic monophosphate
  • cycloheximide
  • receptor regulation

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

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title = "TGF-β1 modulates β-adrenergic receptor number and function in cultured human tracheal smooth muscle cells",
abstract = "Pretreatment of cultured human tracheal smooth muscle cells with transforming growth factor-β1 (TGF-β1) decreased adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by intact cells stimulated with the β- adrenergic agonist isoproterenol. The maximal inhibition of isoproterenol- stimulated cAMP accumulation by TGF-β1 was 31 ± 3{\%}, and the mean effective concentration (EC 50 ) of TGF-β1 was ~1.5 pM. TGF-β1 decreased the maximal response to isoproterenol but did not change the EC 50 value of isoproterenol. TGF-β1 did not change cAMP accumulation stimulated by forskolin. TGF-β1 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-β1 effect is not by direct inhibition of adenylyl cyclase or by decreased activity of the stimulatory GTP-binding protein. Saturation binding experiments with the β-adrenergic receptor radioligand [ 125 I]iodopindolol showed that TGF-β1 pretreatment decreased the β-adrenergic receptor number. The protein synthesis inhibitor cycloheximide abolished the effect of TGF- β1 on both cAMP accumulation and on β-adrenergic receptor number, indicating that protein synthesis is involved. These results suggest that TGF-β1 in the lung could play a role in changing the responsiveness of airway smooth muscle cells to endogenous catecholamines and to β-adrenergic agonists used in therapy.",
keywords = "adenosine 3',5'-cyclic monophosphate, cycloheximide, receptor regulation",
author = "M. Nogami and Debra Romberger and Rennard, {S. I.} and Toews, {Myron Lee}",
year = "1994",
month = "1",
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language = "English (US)",
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pages = "L187--L191",
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T1 - TGF-β1 modulates β-adrenergic receptor number and function in cultured human tracheal smooth muscle cells

AU - Nogami, M.

AU - Romberger, Debra

AU - Rennard, S. I.

AU - Toews, Myron Lee

PY - 1994/1/1

Y1 - 1994/1/1

N2 - Pretreatment of cultured human tracheal smooth muscle cells with transforming growth factor-β1 (TGF-β1) decreased adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by intact cells stimulated with the β- adrenergic agonist isoproterenol. The maximal inhibition of isoproterenol- stimulated cAMP accumulation by TGF-β1 was 31 ± 3%, and the mean effective concentration (EC 50 ) of TGF-β1 was ~1.5 pM. TGF-β1 decreased the maximal response to isoproterenol but did not change the EC 50 value of isoproterenol. TGF-β1 did not change cAMP accumulation stimulated by forskolin. TGF-β1 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-β1 effect is not by direct inhibition of adenylyl cyclase or by decreased activity of the stimulatory GTP-binding protein. Saturation binding experiments with the β-adrenergic receptor radioligand [ 125 I]iodopindolol showed that TGF-β1 pretreatment decreased the β-adrenergic receptor number. The protein synthesis inhibitor cycloheximide abolished the effect of TGF- β1 on both cAMP accumulation and on β-adrenergic receptor number, indicating that protein synthesis is involved. These results suggest that TGF-β1 in the lung could play a role in changing the responsiveness of airway smooth muscle cells to endogenous catecholamines and to β-adrenergic agonists used in therapy.

AB - Pretreatment of cultured human tracheal smooth muscle cells with transforming growth factor-β1 (TGF-β1) decreased adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by intact cells stimulated with the β- adrenergic agonist isoproterenol. The maximal inhibition of isoproterenol- stimulated cAMP accumulation by TGF-β1 was 31 ± 3%, and the mean effective concentration (EC 50 ) of TGF-β1 was ~1.5 pM. TGF-β1 decreased the maximal response to isoproterenol but did not change the EC 50 value of isoproterenol. TGF-β1 did not change cAMP accumulation stimulated by forskolin. TGF-β1 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-β1 effect is not by direct inhibition of adenylyl cyclase or by decreased activity of the stimulatory GTP-binding protein. Saturation binding experiments with the β-adrenergic receptor radioligand [ 125 I]iodopindolol showed that TGF-β1 pretreatment decreased the β-adrenergic receptor number. The protein synthesis inhibitor cycloheximide abolished the effect of TGF- β1 on both cAMP accumulation and on β-adrenergic receptor number, indicating that protein synthesis is involved. These results suggest that TGF-β1 in the lung could play a role in changing the responsiveness of airway smooth muscle cells to endogenous catecholamines and to β-adrenergic agonists used in therapy.

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