A role for ATP in the mechanical activation of nodose C‐fibers in guinea pig lungs

Abstract

Activation of vagal afferent sensory C-fibers in the lungs leads to reflex responses that produce many of the symptoms associated with airway allergy. There are two subtypes of respiratory C-fibers 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-fibers in response to mechanical stimulati in guinea pig lung. We used smooth muscle agonists to induce bronchoconstriction, thereby producing a mechanical stimulus, and found that treatment with both histamine (HA; 30 μM; n=15) and methacholine (MCh; 10 μM; n=4) caused strong action potential discharge in nodose C-fibers (10 ± 2 Hz and 15 ± 8 Hz respectively), but not in jugular C-fibers (n=8). Responses to HA were significantly reduced (P<0.05) by blockade of smooth muscle contraction with isoproterenol (100 μM), suggesting that a component of the response is mechanical in nature. The HA-induced activation of the nodose C-fibers was blocked by pretreatment the H1 receptor antagonist pyrilamine (1 μM; n=5). As ATP activation of P2X3 receptors has been found to play a role in mechanosensory transduction, we examined the effect of P2X3 receptor inhibition on the mechanical activation of nodose C-fibers and found that pretreatment with the P2X3 receptor antagonist AF353 (100 μM; n=5) blocked the response to HA. These results suggest that ATP released within the tissues in response to rapid smooth muscle contraction may play a role in the mechanical activation of nodose C-fibers.