Inhibition by vasoactive intestinal peptide of glycoconjugate and lysozyme secretion by human airways in vitro.
The effects of vasoactive intestinal peptide (VIP) were analyzed on the in vitro release of radioactively labeled mucus glycoconjugates and lysozyme by explants of human bronchial mucosa from normal subjects and from patients with chronic bronchitis. These effects were compared with the effects of VIP on the discharge of labeled macromolecules (analyzed by quantitative autoradiography) from mucous and serous cells of the airway submucosal glands. In explants of 9 mucosal specimens of normal airways, VIP (10 ng to 1 micrograms/ml) caused a dose-dependent inhibition of baseline and methacholine-stimulated release of both glycoconjugates and lysozyme. At a concentration (1 micrograms/ml) that caused maximal inhibition of glycoconjugate and lysozyme release, VIP also caused a small inhibition of baseline but not methacholine-induced discharge of labeled macromolecules from mucous and serous cells of the submucosal glands. In explants from 5 patients with chronic bronchitis, VIP did not inhibit baseline or methacholine-stimulated glycoconjugate release and mucous or serous cell discharge, even at doses greater than 1 micrograms/ml. By contrast, VIP did inhibit baseline and methacholine-stimulated release of lysozyme, but this was less marked than in explants of normal airways. In view of the proximity of neurons containing VIP to submucosal gland cells, this study supported the hypothesis that VIP may contribute to the neurohumoral regulation of mucus secretion by the human airway. It was evident, however, that the effects of VIP could not be accounted for in terms of inhibiting cell discharge alone. In chronic bronchitis, the reduction or absence of sensitivity to VIP inhibition suggests a functional difference in the regulation of mucus secretion, which may contribute to mucus hypersecretion.
D001980:Bronchi / Q000378:metabolism; D001991:Bronchitis / Q000378:metabolism; D046508:Culture Techniques; D005088:Exocrine Glands / Q000187:drug effects; D005260:Female; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D008875:Middle Aged; D009093:Mucus / Q000378:metabolism*; D009113:Muramidase / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D005768:Gastrointestinal Hormones; D046911:Macromolecular Substances; D008688:Methacholine Compounds; D014660:Vasoactive Intestinal Peptide; D009113:Muramidase