Journal of Applied Physiology, Vol 71, Issue 6 2146-2151, Copyright © 1991 by American Physiological Society
Epithelium modulates the potency of vasoactive intestinal peptide in the guinea pig
T. Takubo, K. Banks and J. G. Martin
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
The purpose of the study was to evaluate the importance of the epithelium
in determining the potency of exogenous vasoactive intestinal peptide (VIP)
in inhibiting responses of isolated guinea pig trachea to vagal
stimulation. Isolated innervated tracheal preparations (n = 56) were
mounted in glass organ baths in Krebs-Henseleit (K-H) solution at 37
degrees C and gassed with 95% O2-5% CO2. The inside of the trachea was
separately perfused with K-H solution at 1 ml/min. The vagal nerve trunks
were stimulated (20 V, 1-ms pulses, 10-s trains) at low (0.5 Hz) and high
frequency (15 Hz) alternately, and the contractile responses were measured
as increases in intratracheal pressures. VIP (10(-8)-10(-7) M) inhibited
responses to both high- and low-frequency stimulation. VIP was more potent
in inhibiting contractions when administered to the outside than the inside
surface of the trachea, and disruptionon of the epithelium abolished this
difference. The endopeptidase inhibitors phosphoramidon and thiorphan (5 x
10(-6) M) potentiated the action of VIP. These data indicate that the
epithelium reduces the efficacy of VIP. We suggest that the epithelium is a
site of degradation of VIP by endopeptidase and may also be a diffusion
barrier.
