The effect of tachykinins on transepithelial potential difference (PD) of rabbit trachea and possible involvement of nitric oxide (NO) generation in vivo were investigated. 2. Perfusion of tracheal mucosa with neurokinin A (NKA) or substance P (SP) dose dependently increased PD in the presence of amiloride, with the potency being NKA > SP, but neurokinin B (NKB) had no effect. 3. Application of NG-nitro-L-arginine methylester (L-NAME, 10(-3) M) attenuated the NKA-induced increase in the amiloride-sensitive PD, causing a rightward displacement of the dose-response curve by approximately 1.0 log U, whereas NG-nitro-D-arginine methylester (D-NAME, 10(-3) M) did not. 4. The inhibitory effect of L-NAME was reversed by L-arginine (10(-2) M) but not by D-arginine (10(-2) M). 5. The release of NO was determined by a real-time measurement of NO concentration ([NO]) in the perfusate using specific amperometric sensors for this molecule. 6. NKA and SP increased [NO] in a dose-dependent manner, the maximal increase from the baseline value being 114 +/- 11 nM (mean +/- S.E.M., P < 0.001) and 54 +/- 6 nM (P < 0.01), respectively. 7. Histochemistry for NADPH diaphorase activity showed a strong staining within the epithelial cells. 8. We conclude firstly that tachykinins increase amiloride-sensitive PD in vivo, which probably reflects Cl- movement from the submucosa toward the respiratory lumen in tracheal mucosa, and secondly that NO generation by epithelial cells may be involved in this process.
