Impact and benefit of A(2B)-adenosine receptor agonists for the respiratory tract: mucociliary clearance, ciliary beat frequency, trachea muscle tonus and cytokine release

J Pharm Pharmacol. 2013 Jan;65(1):123-32. doi: 10.1111/j.2042-7158.2012.01580.x. Epub 2012 Aug 16.


Objectives: Adenosine is known to induce a bronchospasm in asthma- and COPD patients. The role of A(2B) receptors was investigated with respect to several parameters of the respiratory tract: tonus of smooth muscle, ciliary beat frequency as measured by high-speed video camera connected to a microscope (both in rats) and mucociliary clearance (MCC; transport of a fluorescent dye using a microdialysis procedure) in mice.

Key findings: NECA (5'-N-ethylcarboxamidoadenosine) (a non-selective adenosine receptor agonist) was able to acutely induce a contraction, which was reversed to a relaxation after repeated dosing. This relaxation was completely abolished by PSB-1115, an A(2B) receptor antagonist. IL-13 (cytokine) was not involved mediating acute contractility effects. MCC was increased by BAY 60-6583 (A(2B) receptor agonist) and NECA (counteracted by the A(2B) receptor antagonist PSB-1115). Activation of A(2B) adenosine receptors by BAY 60-6583 induced an increase of the ciliary beat frequency, which could be reduced by administration of PSB-1115. Several cytokines were increased by NECA although only some are relevant because they are not blocked by A(2B) receptor antagonism.

Conclusions: The A(2B) receptors are involved in airway relaxation, MCC improvement and ciliary beat frequency. A(2B) receptor agonists may be of therapeutic value and should be developed.

MeSH terms

  • Adenosine A2 Receptor Agonists / pharmacology*
  • Aminopyridines / pharmacology
  • Animals
  • Cytokines / metabolism*
  • Drugs, Investigational / pharmacology
  • Female
  • In Vitro Techniques
  • Male
  • Mice
  • Microdialysis
  • Microscopy, Video
  • Microvilli / drug effects
  • Microvilli / metabolism
  • Mucociliary Clearance / drug effects*
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle Tonus / drug effects*
  • Rats
  • Rats, Wistar
  • Receptor, Adenosine A2B / chemistry
  • Receptor, Adenosine A2B / metabolism*
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / metabolism
  • Respiratory System / drug effects*
  • Respiratory System / metabolism
  • Tachyphylaxis
  • Trachea / drug effects
  • Trachea / metabolism


  • Adenosine A2 Receptor Agonists
  • Aminopyridines
  • BAY 60-6583
  • Cytokines
  • Drugs, Investigational
  • Receptor, Adenosine A2B