Tachykinins stimulate nitric oxide generation by canine cultured tracheal epithelium.
We studied the effects of tachykinins on the generation of nitric oxide (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 current 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 effect that was not affected by NG-nitro-D-arginine methylester, but inhibited 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 being 71.0 +/- 14.9 and 33.4 +/- 8.5 nM, respectively (P < 0.001 for each), whereas neurokinin B (NKB) had no effect. In the presence of phosphoramidon, the response of each tachykinin was augmented, but the rank order of potency was still NKA > SP >> NKB. These results suggest that NO is spontaneously released from airway epithelium and that tachykinins stimulate epithelial NO generation via NK2 receptors.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Kondo
M
M
Sakai
A
A
Tagaya
E
E
Takemura
H
H
Konno
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D015288:Neurokinin A / Q000494:pharmacology*; D015287:Neurokinin B / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine; D013373:Substance P / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D006020:Glycopeptides; D018041:Receptors, Neurokinin-2; D009569:Nitric Oxide; D013373:Substance P; D026423:S-Nitroso-N-Acetylpenicillamine; D015288:Neurokinin A; D015287:Neurokinin B; D001120:Arginine; D010396:Penicillamine; C008890:phosphoramidon; D019331:NG-Nitroarginine Methyl Ester