Capsaicin-induced release of VIP-like immunoreactivity: modulation by enzyme inhibitors.
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 [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 min after tracheal infusion of capsaicin were significantly greater in the Thio group than the 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 with 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.
Department of Pathology, Faculty of Medicine, University of São Paulo, Brazil.
A S
AS
Leme
F M
FM
Arantes
E A
EA
Maldonado
M do P
Mdo P
Warth
M A
MA
Martins
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D015244:Thiorphan / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D009498:Neurotoxins; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D016210:Methacholine Chloride; D014660:Vasoactive Intestinal Peptide; D006632:Histamine; D015244:Thiorphan; D002211:Capsaicin