G(s) protein dysfunction in allergen-challenged human isolated passively sensitized bronchi

Am J Physiol Lung Cell Mol Physiol. 2000 Aug;279(2):L209-15. doi: 10.1152/ajplung.2000.279.2.L209.

Abstract

We studied the intracellular mechanisms of allergen-induced beta(2)-adrenoceptor dysfunction in human isolated passively sensitized bronchi. Sensitization was obtained by overnight incubation of bronchial rings with serum containing a high specific IgE level to Dermatophagoides but a low total IgE level. Allergen challenge was done by incubation with a Dermatophagoides mix. The G(s) protein stimulant cholera toxin (2 microg/ml) displaced the carbachol (CCh) concentration-response curves of control and sensitized but not of challenged rings to the right. Cholera toxin (10 microg/ml) displaced the concentration-response curves to CCh of control, sensitized, and challenged rings to the right, but this effect was less in challenged rings. The effects of the G(i) protein inhibitor pertussis toxin (250 ng/ml or 1 microg/ml) on salbutamol concentration-relaxation curves did not differ significantly between challenged and sensitized rings. The adenylyl cyclase activator forskolin and the Ca(2+)-activated K(+)-channel opener NS-1619 relaxed CCh-contracted bronchial rings without significant differences between control, sensitized, and challenged rings. Neither G(i) nor G(s) alpha-subunit expression differed between control, sensitized, and challenged tissues. We conclude that G(s) protein dysfunction may be a mechanism of allergen-induced beta(2)-adrenoceptor dysfunction in human isolated passively sensitized bronchi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Adrenergic beta-Agonists / pharmacology
  • Albuterol / pharmacology
  • Antigens, Dermatophagoides
  • Benzimidazoles / pharmacology
  • Blotting, Western
  • Bronchi / drug effects
  • Bronchi / immunology*
  • Bronchi / metabolism*
  • Bronchoconstriction / drug effects
  • Bronchoconstriction / immunology
  • Carbachol / pharmacology
  • Cholera Toxin / pharmacology
  • Cholinergic Agonists / pharmacology
  • Colforsin / pharmacology
  • Dose-Response Relationship, Drug
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Glycoproteins / immunology*
  • Humans
  • Immunization
  • In Vitro Techniques
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism

Substances

  • Adrenergic beta-Agonists
  • Antigens, Dermatophagoides
  • Benzimidazoles
  • Cholinergic Agonists
  • Glycoproteins
  • Potassium Channels
  • NS 1619
  • Colforsin
  • Carbachol
  • Cholera Toxin
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gs
  • Adenylyl Cyclases
  • Albuterol