James L. Ellis

Neurophysiology of mast cell-nerve interactions in the airways.

The sensitized guinea pig was employed as a model to study the effect of immunological activation of resident mast cells on neuronal activity in the airways. The trachea was isolated with the vagus nerves and vagal sensory ganglia intact. Using conventional electrophysiological recording techniques, we noted that antigenic stimulation led to an increase in the sensitivity of sensory nerve endings located in the airway wall. Moreover, previous work has revealed that antigen challenge potentiates action-potential-driven tachykinin release from afferent fibers in the guinea pig isolated airway. Anatomical and electrophysiological studies indicate that tachykinin-containing sensory fibers directly innervate the local parasympathetic ganglion neurons in the airway. Therefore, antigen-induced increases in the excitability of sensory fibers in the airways can increase parasympathetic tone in the airway by increasing central and peripheral reflex arcs. In addition, we have found that antigen stimulation has direct effects on the excitability of the parasympathetic ganglion neurons. Considered together, the data demonstrate that increased vagal sensory and parasympathetic activity may be a consequence of the allergic reaction in the airways.

Non‐adrenergic, non‐cholinergic contractions in the electrically field stimulated guinea‐pig trachea

1 The effects of drugs and altering stimulus parameters on neurogenic responses to electrical field stimulation (EFS) have been investigated in distal and proximal portions of the guinea‐pig trachea. 2 In the presence of indomethacin (3 μm) and propranolol (1 μm) two contractile phases were evident in both the proximal and distal trachea. The first rapid phase was abolished by atropine (0.1 μm), whereas the prolonged, second phase was abolished by capsaicin (10 μm) pretreatment. Tetrodotoxin (3 μm) abolished the initial response and greatly inhibited the second phase. In proximal trachea this second phase was evident only in 9 of 22 preparations. The addition of the peptidase inhibitor thiorphan (10 μm) however, caused a second phase to be seen in all the proximal tissues examined. 3 The two phases of the contractions to EFS were differentially sensitive to the pulse duration applied. The initial, cholinergic contractions were evident at lower pulse durations than were the prolonged capsaicin‐sensitive contractions, with the first phase being approximately 10 fold more sensitive than the second phase. 4 The magnitude of the capsaicin‐sensitive contraction to EFS was significantly greater in the distal trachea than in the proximal trachea. This difference prevailed in the presence of thiorphan, an inhibitor of neutral endopeptidase. In contrast, concentration‐response curves to capsaicin were similar in segments of proximal and distal trachea. 5 The non‐adrenergic non‐cholinergic (NANC) relaxant responses were studied in tissues in which excitatory neurogenic responses were pharmacologically abolished by capsaicin and atropine treatment. The NANC relaxant responses in the proximal trachea were evident at lower pulse frequencies and were of greater magnitude compared with NANC relaxant responses in the distal trachea. 6 These results indicate that, by pharmacologically manipulating the trachea and by selecting optimum stimulation parameters, a NANC contractile response to EFS can be seen throughout the length of the guinea‐pig trachea. This NANC response is most likely to be due to the release of tachykinins from capsaicin‐sensitive sensory fibres. It is suggested that NANC relaxant responses mask NANC contractile responses especially in the proximal trachea where NANC relaxant responses predominate.