A role for ATP in bronchoconstriction-induced activation of guinea pig vagal intrapulmonary C-fibres

J Physiol. 2012 Aug 15;590(16):4109-20. doi: 10.1113/jphysiol.2012.233460. Epub 2012 Jun 11.

Abstract

Activation of vagal afferent sensory C-fibres in the lungs leads to reflex responses that produce many of the symptoms associated with airway allergy. There are two subtypes of respiratory C-fibres whose cell bodies reside within two distinct ganglia, the nodose and jugular, and whose properties allow for differing responses to stimuli. We here used extracellular recording of action potentials in an ex vivo isolated, perfused lung-nerve preparation to study the electrical activity of nodose C-fibres in response to bronchoconstriction. We found that treatment with both histamine and methacholine caused strong increases in tracheal perfusion pressure that were accompanied by action potential discharge in nodose, but not in jugular C-fibres. Both the increase in tracheal perfusion pressure and action potential discharge in response to histamine were significantly reduced by functionally antagonizing the smooth muscle contraction with isoproterenol, or by blocking myosin light chain kinase with ML-7. We further found that pretreatment with AF-353 or 2',3'-O-(2,4,6-Trinitrophenyl)-adenosine-5'-triphosphate (TNP-ATP), structurally distinct P2X3 and P2X2/3 purinoceptor antagonists, blocked the bronchoconstriction-induced nodose C-fibre discharge. Likewise, treatment with the ATPase apyrase, in the presence of the adenosine A1 and A2 receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and SCH 58261, blocked the C-fibre response to histamine, without inhibiting the bronchoconstriction. These results suggest that ATP released within the tissues in response to bronchoconstriction plays a pivotal role in the mechanical activation of nodose C-fibres.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials
  • Adenosine A1 Receptor Antagonists / pharmacology
  • Adenosine A2 Receptor Antagonists / pharmacology
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Apyrase
  • Bronchial Spasm / chemically induced*
  • Bronchial Spasm / metabolism
  • Guinea Pigs
  • Histamine / pharmacology
  • Male
  • Methacholine Chloride / pharmacology
  • Nodose Ganglion / cytology
  • Nodose Ganglion / physiology
  • Purinergic P2X Receptor Antagonists
  • Receptor, Adenosine A1 / metabolism
  • Receptors, Adenosine A2 / metabolism
  • Receptors, Purinergic P2X / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Culture Techniques
  • Vagus Nerve / physiology*

Substances

  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Purinergic P2X Receptor Antagonists
  • Receptor, Adenosine A1
  • Receptors, Adenosine A2
  • Receptors, Purinergic P2X
  • Methacholine Chloride
  • Histamine
  • Adenosine Triphosphate
  • Apyrase