NERVE-STIMULATION RELEASES MUCOSA-DERIVED INHIBITORY FACTORS, BOTH PROSTANOIDS AND NONPROSTANOIDS, IN ISOLATED FERRET TRACHEA

The influence of an intact mucosa layer in isolated ferret trachea on the contractile responses to repeated, short-lasting (20 s, every 2 min) nerve stimulations was studied in a nerve muscle preparation stimulated to cholinergic-evoked contractions by either direct vagal nerve stimulation (DNS) or transmural electrical field stimulation (EFS). The contractile responses were monitored by three strain gauges connected to the proximal, middle, and distal segments of the trachea. The mucosa was either left intact (M+) or removed from the membranous part by dissection (M-). The successive decrease in contractile responses was studied for 60 min using repeated DNS and for a further 60 min using alternating EFS and DNS. During the first period, in which DNS alone was used, there was a significantly more pronounced decrease in the M+ preparation compared with the M-. This effect was most prominent in the proximal part of the trachea and was not blocked by indomethacin. During the subsequent stimulation period in which alternating EFS and DNS were used, the rate of decrease was significantly greater in all segments. In this phase, however, the inhibitory mucosa-dependent effect was significantly attenuated by indomethacin treatment. In conclusion, this study demonstrates that the mucosa-dependent inhibition or relaxation in ferret trachea is mediated by both a prostanoid and a nonprostanoid factor. The nonprostanoid factor but not the prostanoid factor can be activated by DNS, whereas the release of the prostanoid is activated by EFS, which indicates that the activation of the prostanoid and nonprostanoid factor is controlled by different mechanisms.