Changes in muscarinic cholinergic receptor expression in human peripheral blood lymphocytes in allergic rhinitis patients

Abstract

Background Parasympathetic nerves provide the dominant autonomic innervation of the upper and lower airways. They release acetylcholine that, activating post-junctional muscarinic receptors, causes bronchoconstriction, mucous secretion and vasodilation. Dysfunction of the upper and lower airways frequently coexist, and they appear to share key elements of pathogenesis. Objective The present study has assessed the expression and pattern of cholinergic muscarinic receptor subtypes in peripheral blood lymphocytes harvested from allergic rhinitis patients with different degree of bronchial hyperresponsiveness detected by methacholine challenge test. Methods Radioligand binding assay for determining the density of muscarinic cholinergic receptor subtypes; immunoblot analysis for assessing the characteristic of muscarinic cholinergic receptor subtype protein and immunocytochemical techniques for investigating the cellular localization of receptors. Results An increased expression of M2 and M5 receptor proteins was observed in peripheral blood lymphocytes of allergic rhinitis patients in comparison with healthy control individuals. M3 receptor subtype decreased in allergic rhinitis patients with normal or mild responses to methacholine. A trend versus a return to normal value was found in moderate and severe responders. No changes of the M4 receptor subtype were found. Conclusions and clinical implications Increase in M2 receptor expression correlated with disease severity and bronchial hyperreactivity. Changes in muscarinic cholinergic receptor expression in allergic rhinitis underline a role of cholinergic system of immune cells in allergic airway disease. Capsule summary Studies addressed to rhinitis and asthma have identified many similarities. Our results indicate that changes in peripheral blood lymphocyte muscarinic receptor expression may reflect the cholinergic involvement into allergic airway diseases.