Effect of neuropeptide Y on human bronchus and its modulation of neutral endopeptidase.
BACKGROUND
Neuropeptide Y (NPY) and neutral endopeptidase have been shown to regulate the response of airway smooth muscle. However, their interactions have not been studied.


METHODS
To determine the role of NPY and endogenous neutral endopeptidase in regulating the effects of NPY, we investigated the effects of NPY and a neutral endopeptidase inhibitor, phosphoramidon, on the contractile response of isolated human bronchial segments to electrical field stimulation (EFS).


RESULTS
Concentrations of up to 10(-6) mol/L of NPY did not change resting tension. NPY inhibited the cholinergic contractions induced by EFS at 5 Hz dose-dependently. Phosphoramidon (10(-5) mol/L) enhanced the inhibitory effect of NPY on EFS-induced contractions at 5 Hz. NPY (3 x 10(-7) mol/L) shifted the frequency-response curve for EFS (1 to 50 Hz) to the right and significantly increased the mean logarithm of frequency that produced 50% of maximal contraction (control: 0.54 +/- 0.07 versus NPY: 0.79 +/- 0.09, p < 0.05). Phosphoramidon (10(-5) mol/L) did not affect the frequency response to EFS, but enhanced the inhibitory effect of NPY (3 x 10(-7) mol/L) on frequency response to EFS, resulting in a significant increase in the mean logarithm of frequency that produced 50% of maximal contraction (NPY: 0.79 +/- 0.09 versus NPY plus phosphoramidon: 1.18 +/- 0.15, p < 0.05). NPY (3 x 10(-7) mol/L) did not affect the response of tissues to exogenously applied acetylcholine.


CONCLUSIONS
These observations suggest that NPY inhibits the output of acetylcholine from nerve endings and that endogenous neutral endopeptidase modulates the effect of NPY in the human airway by inactivating this peptide.
Fujiwara
H
H
First Department of Internal Medicine, Osaka City University, Medical School, Japan.
Kurihara
N
N
Hirata
K
K
Ohta
K
K
Kanazawa
H
H
Takeda
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology*
D006020:Glycopeptides; D009478:Neuropeptide Y; D015260:Neprilysin; D000109:Acetylcholine; C008890:phosphoramidon