neurokinin-a and Rhinitis--Allergic--Perennial

In the last decade, several neuropeptides have been localized in sensory, sympathetic and parasympathetic neurons of the upper and lower airways in animals and man. Tachykinins are sensory neuropeptides: after nasal allergen challenge in patients with allergic rhinitis, substance P is locally released and induces nasal obstruction. Like neurokinin A, another tachykinin of sensory C fibers, substance P induces an increase in vascular permeability and a recruitment of inflammatory cells. Thus, tachykinins partially mimic nasal response to antigen. Calcitonin gene-related peptide (CGRP) is another sensory neuropeptide and vasoactive intestinal peptide (VIP) is a neuropeptide localized to parasympathetic fibers. The distributions of CGRP and VIP fibers and of their binding sites, as well as their physiological effects described in other tissues, are consistent with a vasodilator effect. On the other hand, neuropeptide Y (NPY), a sympathetic neuropeptide, would seem to be a potent vasoconstrictor. Thus, nasal neuropeptides, and above all sensory neuropeptides, could play a role in the pathophysiology of allergic rhinitis.

Topics: Allergens; Animals; Calcitonin Gene-Related Peptide; Capillary Permeability; Humans; Mast Cells; Microcirculation; Nasal Mucosa; Neurokinin A; Neuropeptide Y; Neuropeptides; Rats; Rhinitis, Allergic, Perennial; Substance P; Tachykinins; Vasoactive Intestinal Peptide

Recent guidelines reveal that allergic rhinitis impairs quality of life. Neuropeptides play a central role in allergy-related nasal inflammation. The objective of this study was to analyze the release of neuropeptides (substance P, neurokinin A, and vasoactive intestinal peptide) in nasal lavage and their modification by intranasal fluticasone propionate as an established therapy in patients with allergic rhinitis.. Eleven patients with proven allergic rhinitis induced by house dust mite were challenged before and after administration of fluticasone propionate nasal spray. Nasal lavage samples were collected after allergen challenge, and neuropeptides were measured using enzyme-linked immunosorbent assay. Values for histamine, protein, and human serum albumin were also recorded. Eight healthy individuals were included as nonatopic controls.. The neuropeptides investigated were detectable in nasal lavage fluid in both patients and controls. Treatment with fluticasone propionate significantly decreased clinical response to allergen challenge (P < .01) compared with the controls and led to a decrease in values for substance P, neurokinin A, vasoactive intestinal peptide, histamine release, human serum albumin, and total protein after allergen challenge (P < .01).. The demonstration of proinflammatory neuropeptides in NAL and suppression of their release after allergen challenge caused by a topical corticosteroid suggest a role for neuropeptides in allergic inflammation. Diminished release of neuropeptides induced b fluticasone propionate was accompanied by an improvement in the clinical symptoms of patients with persistent allergic rhinitis.

Topics: Adult; Aged; Androstadienes; Anti-Allergic Agents; Antigens, Dermatophagoides; Female; Fluticasone; Histamine; Humans; Male; Middle Aged; Nasal Lavage Fluid; Neurokinin A; Rhinitis, Allergic, Perennial; Serum Albumin; Statistics, Nonparametric; Substance P; Vasoactive Intestinal Peptide; Young Adult

Studies examining the effect of pharmacological agents on respiratory responses to ozone support the concept that the effects are mediated, at least in part, by neural mechanisms, including neuropeptide release. Using a special tissue culture system the influence of ozone (0.1 ppm/24 h) on nasal mucosa from allergic and nonallergic patients undergoing surgery for chronic nasal obstruction was examined. Substance P (SP)-immunoreactive nerves were found in air-exposed as well as in ozone-exposed tissue samples. The content of neurokinin A (NKA) and SP in the culture supernatants was significantly increased following ozone exposure compared to controls. Tissue of allergic patients showed an ozone-induced increase in the release of NKA and SP compared to tissue of nonallergic patients. These results suggest that the mode of action of ozone results in an increased activity of sensory nerves in the upper airways with a subsequent increased release of neuropeptides. In addition to the known ozone-induced release of proinflammatory mediators, these mechanisms may explain the increased responsiveness of patients with hypersensitive airways.

Topics: Biopsy; Culture Techniques; Humans; Immunoenzyme Techniques; Immunohistochemistry; Microscopy, Confocal; Nasal Mucosa; Neurokinin A; Ozone; Rhinitis, Allergic, Perennial; Statistics, Nonparametric; Substance P

To further carry out a quantitative immunohistochemical study on neuropeptides (NPs) participation in perennial allergic rhinitis (PAR) in nasal mucosa.. By using light microscopy (routine hematoxylin and eosin staining, Wright's staining and 1% toluidine blue staining) and scanning as well as transmission electron microscopy, an exhaustive immunohistochemical and morphometric study was made on the changes of substance P (SP), neuropeptide A (NKA) and neuropeptide B (NKB) in the nasal mucosa of a toluene-2,4-iso-cyanate (TDI)-induced PAR model of rat.. The results showed that the densities of all three peptidergic terminals were significantly increased (P < 0.01) in experimental group (115.72 +/- 28.43 for SP, 39.23 +/- 10.34 for NKA and 37.24 +/- 11.22 for NKB, respectively) as compared with those in control group (49.65 +/- 11.23 for SP, 12.44 +/- 6.21 for NKA and 13.31 +/- 7.60 for NKB, respectively). Increased staining, thickening of peptidergic terminals and enlargement of varicosities were found. Mast cell infiltration in nasal mucosa was in parallel with increase of peptidergic terminals.. All results support the hypothesis that NP is a newly-recognized but potentially important factor in the pathogenesis of PAR.

Topics: Animals; Female; Male; Nasal Mucosa; Nerve Endings; Neurokinin A; Neurokinin B; Rats; Rats, Wistar; Rhinitis, Allergic, Perennial; Substance P; Tachykinins; Toluene 2,4-Diisocyanate

To study the density alterations of three peptidergic terminals in nasal mucosa of allergic rhinitis (AR), an exhaustive immunohistochemical sutdy on the changes of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) in nasal mucosa was carried out in a toluene-2, 4-isocyanate (TDI)-induced rat AR model. The densities of all three tachykininergic terminals in nasal mucosa were significantly increased (P < 0.01) in experimental group as compared with control group. Increased staining, thickening of peptidergic terminals as well as enlargement of varicosities were observed. The increased densities of three tachykininergic terminals (SP, NKA and NKB) in nasal mucosa in rat AR model indicates that tachykinins play an important role in the pathogenesis of AR.

Topics: Animals; Female; Immunohistochemistry; Male; Nasal Mucosa; Neurokinin A; Neurokinin B; Rats; Rats, Wistar; Rhinitis, Allergic, Perennial; Substance P; Tachykinins; Toluene 2,4-Diisocyanate