neuropeptide-y 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

Persistent perennial allergic rhinitis belongs to the most frequent diseases in occupational and environmental medicine. Because the innervation may play a role in the pathogenesis of the disease, the present study analyzed nasal mucosal nerve profiles.. Neuropeptide-containing nerve fibers were examined using immunohistochemistry and related to eosinophil and mast cell numbers.. In contrast to constant numbers of mast cells, there was a significant increase in the number of eosinophils. Immunohistochemistry for calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and neuropeptide tyrosine (NPY) revealed abundant staining of mucosal nerves. Semiquantitative assessment of nerve fiber neuropeptide density demonstrated a significant increase of VIP-positive fibers in rhinitis tissues.. The present data indicate a differential regulation of neuropeptide-containing nerve fibers with increased numbers of VIPergic fibers suggesting a modulatory role of the upper airway innervation in perennial allergic rhinitis.

Topics: Adolescent; Adult; Aged; Calcitonin Gene-Related Peptide; Eosinophils; Female; Humans; Leukocyte Count; Male; Mast Cells; Middle Aged; Nasal Mucosa; Nerve Fibers; Neuronal Plasticity; Neuropeptide Y; Occupational Diseases; Reference Values; Rhinitis, Allergic, Perennial; Substance P; Vasoactive Intestinal Peptide

The neuropeptides and neuroendocrine cells are proven to exist in the human nasal mucosa. However, the pathophysiological and neuroimmunological roles of regulatory peptides in human nasal diseases require further investigation.. To investigate and compare the functional morphology and quantify the tissue concentration of regulatory peptides in the nasal mucosas of normal, allergic rhinitis (AR) and chronic hypertrophic rhinitis (CHR) subjects.. Human inferior turbinate mucosa specimens from 28 patients with AR, 25 patients with CHR and 15 patients without any nasal diseases were investigated. Using immunohistochemistry and radioimmunoassays, we detected the presence, distribution and concentrations of various neuropeptides (vasoactive intestinal peptides [VIP], neuropeptide Y [NPY], substance P [SP], calcitonin gene-related peptides [CGRP]) and general neuroendocrine markers (neurone-specific enolase, chromogranin A and somatostatin). Quantitative analysis of the stained fibres and cells were performed using a graphic AutoCAD program.. The presence and distribution of NPY, CGRP, and SP nerve fibres and neuroendocrine cells were similar among the three subject groups. AR subjects had significantly higher VIP and SP tissue concentrations. VIP fibres had highest density in AR subjects and these fibers predominantly innervated vessels. In CHR, VIP fibres primarily innervated glands.. VIP and SP may play an important neuroimmunological role in the pathogenesis of AR. VIP may lead to the hypertrophic changes of submucosal glands in the pathogenesis of CHR.

Topics: Calcitonin Gene-Related Peptide; Humans; Hypertrophy; Nasal Mucosa; Nerve Fibers; Neuropeptide Y; Neuropeptides; Neurosecretory Systems; Radioimmunoassay; Rhinitis; Rhinitis, Allergic, Perennial; Substance P; Turbinates; Vasoactive Intestinal Peptide

Neuroendocrine components exist in the human nasal mucosa. However, the pathophysiological and neuroimmunological roles of the regulatory peptides in allergic rhinitis (AR) require further investigation. To analyse the functional morphology and quantify the tissue concentration of regulatory peptides in the nasal mucosa of AR subjects, human inferior turbinate mucosa specimens from 25 patients with AR, 20 patients with non-allergic rhinitis and 10 patients without any nasal diseases were investigated. Using immunohistochemistry and radioimmunoassays, we detected the presence, distribution and concentrations of various neuropeptides [vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP) and calcitonin gene-related peptide (CGRP)] and general neuroendocrine markers (neuron-specific enolase and chromogranin A). Quantitative analysis of the stained fibres and cells was performed using a graphic AutoCAD program. The presence and distribution of NPY, CGRP and SP nerve fibres and neuroendocrine cells were similar among the three subject groups. AR subjects had significantly higher tissue concentrations of VIP and SP. AR subjects had increased numbers of VIP fibres which predominantly innervated vessels. Thus, VIP and SP play important neuroimmunological roles in the pathogenesis of AR.

Topics: Biomarkers; Calcitonin Gene-Related Peptide; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Nasal Mucosa; Neuropeptide Y; Neuropeptides; Radioimmunoassay; Rhinitis; Rhinitis, Allergic, Perennial; Substance P; Vasoactive Intestinal Peptide

In order to study morphological effects on the nasal and sinus mucosa, New Zealand White rabbits underwent either unselective, regional sectioning of sensory and parasympathetic nerve branches or topical treatment of the mucosa with capsaicin. Ten days after treatment, mucosal specimens were analyzed by light and electron microscopy. Immunohistochemistry was used to evaluate neuropeptides present, in particular substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y. In surgically denervated rabbits, mucosal glands were found to be enlarged and contained an increased number of zymogen granules having a bipartite substructure. Topical capsaicin application caused localized epithelial changes in the sinus mucosa and maxilloturbinal region of the nose, including clotting of cilia and an increased number of goblet cells. Reduced amounts of all neuropeptides investigated were found in the surgically denervated animals, while topical capsaicin treatment had only marginal effects on the mucosal neuropeptide content. The morphological changes observed after surgical denervation suggest an imbalance between neural stimulation and secretory capacity of the mucosal glands. These findings could explain the difference in clinical effect noted between sectioning of the vidian nerve and topical treatment with capsaicin in patients with perennial rhinitis.

Topics: Administration, Topical; Animals; Autonomic Nervous System; Calcitonin Gene-Related Peptide; Capsaicin; Cytoplasmic Granules; Denervation; Fluorescent Antibody Technique; Microscopy, Electron; Nasal Mucosa; Neuropeptide Y; Neuropeptides; Paranasal Sinuses; Rabbits; Rhinitis, Allergic, Perennial; Substance P; Trigeminal Nerve; Vasoactive Intestinal Peptide

Neuropeptide Y (NPY) is a neurotransmitter in sympathetic nerve fibers in human nasal mucosa. Like norepinephrine, NPY acts as a vasoconstrictor. An established method of nasal provocation was used to determine the effects of topically applied NPY on nasal resistance to airflow measured by anterior rhinomanometry, the protein content of nasal secretions, and the protein content of bradykinin-induced secretions. NPY (2.3 nmol) reduced the resistance to inspiratory airflow by 57 +/- 18% (P < 0.001) in 10 normal subjects and by 50 +/- 17% (P < 0.05) in 12 subjects with perennial rhinitis. In nasal provocations, NPY in doses of 0.1-10 nmol had no effect on vascular (albumin), glandular (lysozyme, glycoconjugate), or total proteins present in lavaged nasal secretions. Because the vasoconstrictor properties of NPY may only be apparent in the presence of increased vascular permeability and albumin exudation, bradykinin (BK) nasal provocation was performed. BK (500 nmol) significantly increase total protein (10- to 20-fold), albumin (10- to 30-fold), and glycoconjugate (2- to 5-fold) in lavage fluid. NPY (2.3 nmol) reduced BK-induced total protein by 59 +/- 15% (P < 0.05) and albumin by 63 +/- 17% (P < 0.02) but had no significant effect on glandular secretion. Therefore exogenous administration of NPY to the human nasal mucosa reduced nasal airflow resistance and albumin exudation without affecting submucosal gland secretion. NPY agonists may be useful for the treatment of mucosal diseases characterized by vasodilation, vascular permeability, and plasma exudation.

Topics: Adult; Airway Resistance; Albumins; Bradykinin; Capillary Permeability; Dose-Response Relationship, Drug; Glycoconjugates; Humans; Manometry; Middle Aged; Muramidase; Nasal Decongestants; Nasal Mucosa; Nasal Provocation Tests; Neuropeptide Y; Proteins; Regional Blood Flow; Rhinitis, Allergic, Perennial