Capsaicin-induced release of vasoactive intestinal peptide-like
immunoreactivity: modulation by enzyme inhibitors.
Leme, Adriana S., Fernanda M. Arantes, Edna A. L. Maldonado, Maria Do
Patroc[acute]inio T. N. Warth, and Milton A. Martins.
Departments of Pathology and Medicine, Faculty of Medicine,
University of Sao Paulo, Brazil
APStracts 3:0089L, 1996.
Vasoactive intestinal peptide (VIP) is a potent bronchial smooth
muscle relaxant. In the present study we measured the release of VIP
-like immunoreactivity (VIP-LI) after tracheal infusion of capsaicin,
histamine and methacholine in isolated guinea pig lungs superfused
through the trachea. We also studied if inhibition of VIP enzymatic
cleavage using a combination of an inhibitor of neutral endopeptidase
(NEP) (thiorphan, THIO) and an inhibitor of serine proteases (soybean
trypsin inhibitor, STI) influenced the airway effects of capsaicin.
Infusion of capsaicin resulted in a significant increase in VIP-LI in
the perfusate (12.32 +/- 4.80 to 33.52 +/- 8.46 fmol/5 min-fraction,
P < 0.001). There was no increase in VIP-LI after infusion of
methacholine or histamine. Maximal changes in airway opening pressure
(Pao) observed 0-10 minutes after tracheal infusion of capsaicin were
significantly greater in THIO group than control group and the groups
of lungs that received STI or STI+THIO (P < 0.005). In addition,
recovery of VIP-LI in the superfusate after infusion of capsaicin was
significantly greater in the group of lungs that was superfused with
THIO+STI compared to STI, THIO and control groups. Our results
suggest that a bronchodilator peptide with the profile of enzymatic
cleavage of VIP also modulates capsaicin effects, since the increase
in Pao in the presence of THIO+STI was significantly lower than THIO
alone.
Received 7 August 1995; accepted in final form 20 May 1996.
APS Manuscript Number L247-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96