ROLE OF NITRIC-OXIDE IN TACHYKININ-INDUCED INCREASE IN POTENTIAL DIFFERENCE OF RABBIT TRACHEAL MUCOSA

1. The effect of tachykinins on transepithelial potential difference ( PD) of rabbit trachea and possible involvement of nitric oxide (NO) ge neration in vivo were investigated. 2. Perfusion of tracheal mucosa wi th neurokinin A (NKA) or substance P (SP) dose dependently increased P D in the presence of amiloride, with the potency being NKA > SP, but n eurokinin B (NKB) had no effect. 3. Application of N-G-nitro-L-arginin e methylester (L-NAME, 10(-3) M) attenuated the NKA-induced increase i n the amiloride-sensitive PD, causing a rightward displacement of the dose-response curve by approximately 1.0 log U, whereas N-G-nitro-D-ar ginine 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 measur ement of NO concentration ([NO]) in the perfusate using specific amper ometric sensors for this molecule. 6. NKA and XP increased [NO] in a d ose-dependent manner, the maximal increase from the baseline value bei ng 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 t hat tachykinins increase amiloride-sensitive PD in vivo, which probabl y reflects Cl- movement from the submucosa toward the respiratory lume n in tracheal mucosa, and secondly that NO generation by epithelial ce lls may be involved in this process.