neuropeptide-y and Rhinitis

Topics: Bradykinin; Calcitonin Gene-Related Peptide; Cytokines; Eicosanoids; Histamine H1 Antagonists; Humans; Nasal Mucosa; Nasal Polyps; Neurokinin A; Neuropeptide Y; Platelet Activating Factor; Receptors, Calcitonin Gene-Related Peptide; Rhinitis; Substance P; Vasoactive Intestinal Peptide

Recent research has disclosed that neurotransmitters and neuropeptides released within the autonomic nervous system exert homeostatic control of nasal secretion. Although cholinergic and adrenergic influences have long been thought to be the predominant mechanisms, the nonadrenergic, noncholinergic responses may have more suitable, longer-lasting effects. Peptides from sensory nerves, such as calcitonin gene related peptide, substance P, and neurokinin A, may participate in axon response-mediated vasodilation and plasma extravasation. Substance P and gastrin releasing peptide may induce glandular secretion. Defensive responses to local mucosal injury may be amplified by axon response, which initiates these vascular and glandular reactions. Cholinergic effects are primarily responsible for mediating parasympathetic reflexes, but vasoactive intestinal peptide may regulate acetylcholine release, augment glandular secretory responses, and have a vasodilatory effect. In the sympathetic nervous system, neuropeptide Y probably functions as a long-acting vasoconstrictor. Integration of sympathetic and parasympathetic influence may regulate the normal nasal cycle, and sensory and parasympathetic defensive reflexes may respond to epithelial and mast cell stimulation. It is possible, then, that the pathophysiology of vasomotor rhinitis involves an exaggeration of these neural influences.

Topics: Animals; Calcitonin Gene-Related Peptide; Gastrin-Releasing Peptide; Gastrointestinal Hormones; Humans; Nasal Mucosa; Nervous System Physiological Phenomena; Neuropeptide Y; Neuropeptides; Peptides; Rhinitis; Tachykinins; Vasoactive Intestinal Peptide

Bitter taste receptors (T2Rs) are G-protein-coupled receptors (GPCRs) expressed on the tongue but also in various locations throughout the body, including on motile cilia within the upper and lower airways. Within the nasal airway, T2Rs detect secreted bacterial ligands and initiate bactericidal nitric oxide (NO) responses, which also increase ciliary beat frequency (CBF) and mucociliary clearance of pathogens. Various neuropeptides, including neuropeptide tyrosine (neuropeptide Y or NPY), control physiological processes in the airway including cytokine release, fluid secretion, and ciliary beating. NPY levels and/or density of NPYergic neurons may be increased in some sinonasal diseases. We hypothesized that NPY modulates cilia-localized T2R responses in nasal epithelia. Using primary sinonasal epithelial cells cultured at air-liquid interface (ALI), we demonstrate that NPY reduces CBF through NPY2R activation of protein kinase C (PKC) and attenuates responses to T2R14 agonist apigenin. We find that NPY does not alter T2R-induced calcium elevation but does reduce T2R-stimulated NO production via a PKC-dependent process. This study extends our understanding of how T2R responses are modulated within the inflammatory environment of sinonasal diseases, which may improve our ability to effectively treat these disorders.

Topics: Apigenin; Calcium; Cells, Cultured; Cilia; Humans; Nasal Mucosa; Neuropeptide Y; Nitric Oxide; Nitric Oxide Synthase Type III; Protein Kinase C; Receptors, G-Protein-Coupled; Receptors, Neuropeptide Y; Rhinitis; Sinusitis

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

An immunohistochemical study of the nasal mucosa was done in pediatric patients attending an otorhinolaringology (ORL) clinic. The goal was a comparison between vascular innervation in patients with or without symptoms of chronic rhinitis. All patients had an indication for tonsillectomy prior to their inclusion in this study. Samples were obtained under general anesthesia at the time of programmed surgery and fixed in a paraformaldehyde-picric acid mixture. Cryostat sections were immunostained for the following neuronal markers: protein-gene product 9.5 (PGP), calcitonin gene- related peptide (CGRP), substance P (SP), and C-terminal peptide of neuropeptide Y (CPON). The following classes of vessels were identified: arteries, sinusoids, veins, and arteriovenous anastomoses (AVAs). As shown by immunostaining with the general neuronal marker PGP, each vessel type had a characteristic innervation pattern, differing in the amount of fibers and their distribution within the adventitial and muscle layers. Evaluation of PGP, CPON, and CGRP immunoreactivity patterns indicated that rhinitic arteries and AVAs displayed a richer innervation than did nonrhinitic blood vessels. Quantification of vascular PGP immunostaining confirmed the difference of vascular innervation between nonrhinitic and rhinitic patients. Fibers immunostained by CPON partially accounted for the rhinitic arterial hyperinnervation.

Topics: Arteries; Arteriovenous Anastomosis; Blood Vessels; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Chronic Disease; Humans; Immunohistochemistry; Nasal Mucosa; Nerve Fibers; Nerve Tissue Proteins; Neuropeptide Y; Peptide Fragments; Rhinitis; Substance P; Thiolester Hydrolases; Turbinates; Ubiquitin Thiolesterase

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

This study aims to investigate the roles of neuropeptides in the pathophysiology of human nasal diseases. By using immunohistochemistry and radioimmunoassay, we detected the presence, distribution and concentrations of the following neuropeptides in human nasal tissue: vasoactive intestinal peptides (VIP), neuropeptide Y (NPY), substance P (SP), and calcitonin gene-related peptides (CGRP). This was performed in human nasal inferior turbinate mucosa from 20 patients with allergic rhinitis, twenty-five patients with chronic hypertrophic rhinitis and 10 patients without any nasal disease conditions. The presence and distribution of NPY. CGRP and SP fibers among the three subject groups displayed no evident differences. VIP fibers were densely stained around the vessels in the allergic group. In contrast, these fibers were more prominently distributed around the submucosal glands of the chronic hypertrophic rhinitis group. The concentration of VIP and SP in human nasal inferior turbinate showed a significant increase in allergic subjects. Thus, VIP may be revelant to the hypertrophic changes of the nasal mucosa. Both SP and VIP may play significant neuroimmunological roles in the pathogenesis of allergic rhinitis.

Topics: Calcitonin Gene-Related Peptide; Humans; Hypertrophy; Nasal Mucosa; Neuropeptide Y; Nose Diseases; Respiratory Hypersensitivity; Rhinitis; Substance P; Vasoactive Intestinal Peptide