TACHYKININS STIMULATE NITRIC-OXIDE GENERATION BY CANINE CULTURED TRACHEAL EPITHELIUM

We studied the effects of tachykinins on the generation of nitric oxid e (NO) from canine cultured tracheal epithelial cells using a specific amperometric sensor for this molecule. Immersion of the NO-selective electrode in the medium bathing the cells detected the baseline curren t of 30.5-61.7 pA, which corresponded to NO concentration ([NO]) at 44 .0 +/- 7.6 nM (mean +/- S.E.M.). Substance P (SP, 10(-6) M) increased the current from 51.3 +/- 9.8 to 73.6 +/- 11.4 pA (P < 0.001), an effe ct that was not affected by NG-nitro-D-arginine methylester, but inhib ited by NG-nitro-L-arginine methylester by 83 +/- 9% (P < 0.001), and this inhibition was restored by the subsequent addition of L-arginine, but not by D-arginine. SP and neurokinin A (NKA) increased [NO] in a dose-dependent manner, the maximal increases from the baseline level b eing 71.0 +/- 14.9 and 33.4 +/- 8.5 nM, respectively (P < 0.001 for ea ch), whereas neurokinin B (NKB) had no effect. In the presence of phos phoramidon, the response of each tachykinin was augmented, but the ran k order of potency was still NKA > SP much greater than NKB. These res ults suggest that NO is spontaneously released from airway epithelium and that tachykinins stimulate epithelial NO generation via NK2 recept ors.