Neutral endopeptidase activity and concentration of sensory neuropeptide in the human nasal mucosa

Abstract

Human nasal mucosa biopsy samples were studied by biochemical and histological methods to determine whether the concentration of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) as a marker of sensory nerves was dependent on the activity of neutral endopeptidase-like enzyme (NEP-LE). Mucosal samples from the middle turbinate were obtained from 32 patients undergoing functional endoscopic nasal surgery for non-allergic chronic rhinosinusitis. The degree of symptoms related to nasal obstruction, rhinorrhea and headaches was recorded. The number of inflammatory cells in each biopsy sample was evaluated by conventional histopathological examination. CGRP-LI was measured by radioimmunoassay. The activity of NEP-LE was evaluated in vitro using [3H] Leu5-enkephalin as substrate. A good correlation was observed between increased concentrations of CGRP, abundant inflammatory cells and the intensity of symptoms (R2 = 0.80). A low activity of NEP-LE was associated with a high concentration of both inflammatory cells and CGRP, suggesting that NEP-LE activity was reduced during inflammation. These observations further support the hypothesis that reduced degradation of sensory neuropeptides could be involved in the pathophysiological mechanisms of non-specific chronic rhinosinusitis.

Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis

“…[23][24][25][26][27][28] Nasal provocation studies in PNAR have shown that a positive response may exist despite a negative skin test and/or serum specific IgE. [29][30] Additional studies have shown the presence or synthesis of IgE in the nasal mucosa.…”

Intranasal administration of neuropeptide Y in man: systemic absorption and functional effects

“…NPY is a substrate for neutral endopeptidase (NEP) (Baraniuk et al, 1990). NEP-like enzyme activity is reduced in patients with non-specific chronic rhinosinusitis (Lacroix et al, 1995), suggesting that both biological activity and intranasal absorption of exogenous NPY could be increased in these patients. This issue is currently under study.…”

Capsaicin treatment of idiopathic rhinitis: The new panacea?

“…In spite of the CGRP-Li reduction demonstrated by Lacroix et al [26], we found no significant difference in pan-neurogenic staining of nasal mucosa using microfilament and synaptophysine between capsaicin and placebo-treated patients 2 weeks, 3 months, and 9 months after therapy, although there was a significant therapeutic effect measured with visual analogue scale (VAS) [8]. Also, Wolf et al [46] were unable to show a reduction of NANC fibers in the nasal mucosa in IR patients after successful capsaicin treatment.…”

“…Treatment of the rat bladder with capsaicin results in a striking downregulation of VR1 expression, accompanied by a loss of SP and CGRP [40,41]. The hypothesis that a hyperactive nonadrenergic, noncholinergic, peptidergic neural system is the underlying pathophysiology in IR was corroborated by Lacroix et al [26], who reported an increased concentration of neuropeptides in a group of chronic IR patients, improvement of symptoms by local treatment of capsaicin giving a 50% reduction in CGRP-Li (CGRP-like immunoreactivity) content in nasal biopsies [42], and a correlation between symptom intensity and CGRP-Li concentration in nasal mucosa [43]. Several studies have been published showing a therapeutic effect in IR patients for repeated topical applications of capsaicin [44][45][46].…”

“…These neuropeptides, which are locally released from peptidergic neurons (antidromic release), mainly unmyelinated sensory C-fibers in the nasal mucosa after activation by unspecific stimuli and degraded by endopeptidase [23], might contribute to the symptoms of IR [24][25][26]. Stimulation can be induced by inf lammatory mediators, such as histamine and bradykinin, but also by a number of inhaled irritants, such as nicotine, cigarette smoke, formaldehyde, and capsaicin [27,28].…”