Apyrase (APY) inhibits mechanical activation of nodose C‐fibers in guinea pig lung

Abstract

Vagal sensory C‐fiber activation in the lungs leads to symptoms of airway diseases. The two subtypes of vagal respiratory C‐fibers have cell bodies in either the nodose or jugular ganglia. We have shown that nodose, but not jugular C‐fibers, are strongly activated by histamine (HA) and methacholine (MCh), responses that are inhibited by blocking smooth muscle contraction (ML‐7 or isoproterenol), and nearly abolished by two structurally unrelated P2X3‐P2X2/3 receptor antagonists (AF‐353 or TNP‐ATP). We hypothesized that the C‐fibers are activated by ATP released during airway smooth muscle contraction, and independently addressed this hypothesis using the enzyme APY to metabolize ATP. We recorded action potential (AP) discharge from single nodose C‐fibers in an ex vivo isolated perfused guinea pig lung nerve preparation exposed to HA (30 μM) before and after APY. APY alone (5 or 10 U/ml) had no effect on HA‐induced AP discharge (n=4 P>0.1). We hypothesized that ATP hydrolysis produced adenosine (ADO; activates nodose C‐fibers). Blocking ADO receptors (A1, DPCPX 100 nM; A2, SCH58261 100 nM) had no effect on HA‐induced AP discharge (n=3, P>0.1), but in the presence of ADO receptor blockade, APY (5 U/mL) nearly abolished the response to HA (14 ± 3 to 3 ± 0 Hz, P <0.05 n=4). These results provide additional evidence that ATP released from the tissues plays a pivotal role in the mechanical activation of nodose C‐fibers.