vasoactive-intestinal-peptide 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

Mucociliary clearance (MCC) is the primary physical airway defense against inhaled pathogens and particulates. MCC depends on both proper fluid/mucus homeostasis and epithelial ciliary beating. Vasoactive intestinal peptide (VIP) is a neurotransmitter expressed in the sinonasal epithelium that is up-regulated in allergy. However, the effects of VIP on human sinonasal physiology are unknown, as are VIP's interactions with histamine, a major regulator of allergic disease. We imaged ciliary beat frequency, mucociliary transport, apical Cl(-) permeability, and airway surface liquid (ASL) height in primary human sinonasal air-liquid-interface cultures to investigate the effects of VIP and histamine. VIP stimulated an increase in ciliary beat frequency (EC50 0.5 μM; maximal increase ∼40% compared with control) and cystic fibrosis transmembrane conductance regulator (CFTR)-dependent and Na(+)K(+)2Cl(-) cotransporter-dependent fluid secretion, all requiring cAMP/PKA signaling. Histamine activated Ca(2+) signaling that increased ASL height but not ciliary beating. Low concentrations of VIP and histamine had synergistic effects on CFTR-dependent fluid secretion, revealed by increased ASL heights. An up-regulation of VIP in histamine-driven allergic rhinitis would likely enhance mucosal fluid secretion and contribute to allergic rhinorrhea. Conversely, a loss of VIP-activated secretion in patients with CF may impair mucociliary transport, contributing to increased incidences of sinonasal infections and rhinosinusitis.

Topics: Calcium Signaling; Chlorides; Cilia; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cystic Fibrosis Transmembrane Conductance Regulator; Drug Synergism; Histamine; Humans; Ion Transport; Nasal Mucosa; Primary Cell Culture; Rhinitis; Sodium-Potassium-Chloride Symporters; Vasoactive Intestinal Peptide

Secretion of calcitonin gene-related peptide (CGRP) from trigeminal nerves and vasoactive intestinal peptide (VIP) from parasympathetic nerves is involved in the pathophysiology of migraine and rhinosinusitis. Analysis of these neuropeptides in human saliva samples can be used as markers of trigeminal and parasympathetic nerve activity in patients between and during attacks as well as in response to specific treatments.. To compare the amount of trigeminal sensory and parasympathetic nerve activation by measuring CGRP and VIP levels in the saliva of subjects experiencing noninfectious allergic rhinosinusitis, migraine with sinus symptoms, and no symptoms.. Subjects were enrolled in three groups. Group A: subjects without a history of migraine, "sinus" headache, or allergic rhinosinusitis within the previous 6 months. Group B: subjects with chronic recurrent noninfectious rhinosinusitis and no history of migraine or "sinus" headache. Group C: subjects with self-described "sinus" headaches whose symptoms met International Headache Society diagnostic criteria (1.1 or 1.2) for migraine. The total amount of CGRP and VIP present in saliva collected under normal, pathological, and therapeutic conditions was determined by radioimmunoassay. Neuropeptide levels were normalized to total volume and amount of protein, and levels were correlated to onset and change in clinical symptoms.. Total volume, total protein, and CGRP and VIP levels did not significantly change in saliva collected on consecutive days in the clinic and at the subject's home, respectively. No appreciable change in baseline salivary levels of CGRP and VIP was detected in control subjects. However, baseline salivary levels of CGRP and VIP were significantly elevated between attacks in allergic rhinosinusitis and migraine subjects compared to control values. For rhinosinusitis subjects, the amount of CGRP and VIP during attacks returned to baseline values following treatment with pseudoephedrine and relief of symptoms. Similarly, CGRP and VIP levels during a migraine headache were significantly reduced within 2 hours after sumatriptan treatment and reported symptom relief.. Correlation of CGRP and VIP saliva levels observed in our study supports physiologically coordinated regulation of trigeminal and parasympathetic nerve activation in allergic rhinosinusitis and migraine patients between and during attacks as well as following treatment. Furthermore, our findings demonstrate that analysis of human saliva neuropeptides may provide a semiquantitative index of pathological and therapeutic states and, therefore, function as a clinical model for studying neuronal mechanisms involved in migraine and rhinosinusitis.

Topics: Adolescent; Adult; Calcitonin Gene-Related Peptide; Ephedrine; Female; Humans; Male; Middle Aged; Migraine Disorders; Neuropeptides; Parasympathetic Nervous System; Rhinitis; Saliva; Salivary Proteins and Peptides; Sinusitis; Sumatriptan; Trigeminal Nerve; Vasoactive Intestinal Peptide; Vasoconstrictor Agents

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

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

The purpose of this study was to determine whether nasal inflammation is present in patients with obstructive sleep apnea (OSA). The number of polymorphonuclear leukocytes (PMNs) and the concentrations of bradykinin and vasoactive intestinal peptide (VIP) were quantified in nasal lavage fluid of eight nonsmoking patients with OSA and in six matched controls before sleep and the next morning. The total number of cells and the percentage of PMNs was significantly higher in patients with OSA in comparison to controls before and after sleep (P < .05). Likewise, bradykinin and VIP concentrations were significantly higher in patients with OSA in comparison to controls before and after sleep (P < .05). These findings indicate that nasal inflammation is present in patients with OSA. We suggest that nasal inflammation plays a role in upper airway obstruction in OSA.

Topics: Adult; Airway Obstruction; Bradykinin; Female; Humans; Leukocyte Count; Male; Middle Aged; Nasal Lavage Fluid; Neutrophils; Polysomnography; Rhinitis; Sleep Apnea Syndromes; Vasoactive Intestinal Peptide