Release of inflammatory mediators from guinea pig trachea by electrical field stimulation: Lack of neuronal involvement

Electrical field stimulation (EFS; 5-10 V, 1 ms, 20 Hz for 1 min) of isolated guinea pig trachea resulted in a rapid increase in tone that is blocked by either atropine or tetrodotoxin (TTX). EFS of tracheal spirals also caused large increases in the release of certain prostanoids with release of prostaglandin (PG)D₂, PGE₂ and PGF(2α) (16.5-, 3.0- and 4.1- fold, respectively). In contrast to the smooth muscle response, however, EFS- induced release of prostanoids was not significantly altered in the presence of TTX. Removal of the epithelium reduced the amount of prostanoids released by EFS. Thus, EFS-induced production of PGD₂, PGE₂ and PGF(2α) was significantly reduced by about 30%, 70% and 80% in epithelium-denuded tissues, respectively. Direct vagal stimulation caused a rapid contraction of the trachealis but failed to elicit increases in the release of histamine or arachidonic acid metabolites. Furthermore, the selective stimulant of C-type sensory fibers capsaicin (3 μM) or exogenously applied substance P (1 μM) or neurokinin A (1 μM) failed to induce histamine, leukotriene or prostanoid release from guinea pig tracheal rings. Although, the mechanism involved in stimulation of arachidonic acid metabolism by EFS is unclear, this effect in part involves the epithelium but apparently is not mediated by airway elements sensitive to TTX, direct vagal stimulation or tachykinins.