Expression and Localization of Purinergic P2Y12 Receptor in Human Nasal Mucosa

ABSTRACTBackgroundExtracellular nucleotides such as ATP and UTP are released from essentially all cells, and they interact with cell surface P2 receptors to produce a broad range of physiological responses. P2Y12 receptor is the major platelet receptor that mediates ADP-induced aggregation, P2Y12 receptor inhibitors such as clopido- grel and prasugrel inhibit platelet aggregation, and thus, they are used in the treatment and prevention of coronary artery disease. Recently, studies have focused on the P2Y12 receptor as a receptor for leukotriene E4 (LTE4), because this receptor is required for LTE4-mediated pulmonary inflammation. To establish the presence of P2Y12 receptor in human nasal mucosa, we investigated the expression and the localization of the P2Y12 receptor in human nasal mucosa.MethodsHuman turbinates were obtained by turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. The expression of P2Y12 receptor was evaluated by RT-PCR, western blotting, and immu- nohistochemical analysis.ResultsRT-PCR analysis of total RNA extracted from human nasal turbinate, primary cultured human nasal epithelial cells and nasal vascular endothelial cells demonstrated the expression of P2Y12 receptor mRNA. A band of approximately 55kDa was detected in human turbinates by western blot analysis using anti-P2Y12 receptor antibody. We could not find any differences between P2Y12 receptor levels in allergic and non-allergic nasal mucosa. An immunohistochemical study revealed that epithelial cells, submucosal glands and vascular endothelial cells showed intense immunoreactivity for the P2Y12 receptor.ConclusionsThe results may have important clinical implications for understanding the role of P2Y12 receptor in upper airway diseases such as allergic rhinitis and non-allergic rhinitis