The effect of sensory nerve depletion on cholinergic neurotransmission in guinea pig airways.

C-fiber primary afferent sensory nerves, containing neuropeptides such as substance P and neurokinin A, mediate excitatory nonadrenergic, noncholinergic (e-NANC) bronchoconstrictor responses in guinea pigs. We have studied the effects of sensory nerve depletion in vivo and at four different airway levels in vitro. Capsaicin pretreatment significantly reduced the cholinergic responses to electrical field stimulation at all airway levels studied when compared to similar responses obtained in tissues from both untreated animals and animals treated with the vehicle for capsaicin (at 8 Hz, 27.2 +/- 4.9% of maximal contraction to 10(-2) M acetylcholine in lower trachea from vehicle-pretreated animals compared with 11.6 +/- 2.9% in lower trachea from capsaicin-pretreated animals, P less than .01). Stimulation of lower tracheal segments at 30-min intervals revealed a cholinergic response which was followed by a small, delayed e-NANC component. In vivo cholinergic bronchoconstrictor responses to vagal stimulation were also significantly diminished (at 5 Hz from 11.6 +/- 2.2 cm H2O in vehicle-pretreated animals to 3.3 +/- 1.4 cm H2O in capsaicin-pretreated animals). Bronchoconstrictor responses to acetylcholine or substance P in normal, vehicle-pretreated or capsaicin-pretreated animals were not significantly different either in vitro or in vivo. Sensory neuropeptides released from C-fiber afferent nerves may facilitate cholinergic neurotransmission in airways. This effect appears more marked at airway levels in which e-NANC responses are demonstrable.