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The information sent from these afferent terminals is digitally encoded in the form of action potentials, integrated in the brainstem, and ultimately leads to sensations GPX4 such as the urge to cough and dyspnoea, as well as various reflex outputs such as changes in breathing pattern, heart rate and blood pressure, cough, airway constriction, mucus secretion, mucosal oedema and inflammatory cell chemotaxis (Coleridge & Coleridge, 1994; Taylor-Clark & Undem, 2006; Lee, 2009). Together, these respiratory sensations and reflex responses serve important roles in maintaining physiological homeostasis and in defending the pulmonary system, necessary for its vital function of gas exchange (Lee & Pisarri, 2001; Bessac & Jordt, 2008). The majority of nerve fibres innervating the respiratory Osimertinib solubility dmso tract are bronchopulmonary C fibres. One of the defining features of these C fibre afferents is the expression of transient receptor potential vanilloid receptor type 1 (TRPV1; Geppetti et al. 2006; Lee & Gu, 2009). The function of TRPV1 as a transducer for multiple physiological and environmental stimuli has been well recognized. It is activated not only by vanilloid molecules, including capsaicin, but also by protons, hyperthermia, anandamide and certain lipoxygenase metabolites of arachidonic acid (Caterina & Julius, 2001; Pingle et al. 2007). The important role of these TRPV1-expressing C fibre sensory nerves in the regulation of cardiopulmonary function in both normal and abnormal conditions has been well documented (Coleridge & Coleridge, 1994; Lee & Pisarri, 2001; Takemura et al. 2008; Lee, 2009). Extracellular calcium-sensing receptor (CaSR), first isolated from bovine parathyroid in 1993, is a G protein-coupled receptor that monitors the systemic, extracellular, free ionized calcium level in organs involved in systemic calcium homeostasis (Brown et al. 1993; Brown & MacLeod, 2001). Calcium-sensing receptor regulates the Ca2+ balance largely by regulating parathyroid hormone secretion by the parathyroid gland, calcitonin secretion by the thyroid gland, Ca2+ excretion by the kidneys, and osteoblast Alectinib proliferation and differentiation (Brown & MacLeod, 2001). In addition to activation by Ca2+, CaSR is also activated by a variety of compounds, including other di- and trivalent cations, polyamines, aminoglycoside antibiotics, calcimimetics, l-amino acids and polypeptides (McLarnon & Riccardi, 2002; Jensen & Br?uner-Osborne, 2007; Yang et al. 2009; Magno et al. 2011). It has recently become apparent that CaSR is widely expressed in tissues with functions not directly related to the regulation of plasma Ca2+, suggesting that CaSR regulates a variety of processes independent of systemic Ca2+ homeostasis (Brown & MacLeod, 2001; Magno et al. 2011). A role of CaSR in taste transduction and perception has recently been indicated (Ohsu et al. 2010).