title: Impact and benefit of A(2B)-adenosine receptor agonists for the respiratory tract: mucociliary clearance, ciliary beat frequency, trachea muscle tonus and cytokine release.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Pharmacology, Institute of Medicinal Chemistry, University of Muenster, Muenster, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Walaschewski
authors.forename: Frank
authors.initials: F
authors.lastname: Begrow
authors.forename: Eugen J
authors.initials: EJ
authors.lastname: Verspohl
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D015507:Drugs, Investigational / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D017551:Microdialysis; D018715:Microscopy, Video; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009079:Mucociliary Clearance / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D043704:Receptor, Adenosine A2B / Q000737:chemistry / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism; D013618:Tachyphylaxis; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D000631:Aminopyridines; C518875:BAY 60-6583; D016207:Cytokines; D015507:Drugs, Investigational; D043704:Receptor, Adenosine A2B