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We carried out another series of experiments to investigate whether the effect of CaSR activation can be abolished by CaSR antagonist. Indeed, our results showed that pretreatment with a mixture of CaSR agonist NPS R-568 (0.5 ��m) LEE011 and antagonist NPS 2143 (10 ��m) failed to affect the capsaicin-evoked inward current in bronchopulmonary sensory neurons (Fig. 6; P > 0.05, n= 7). Extracellular Ca2+ is, of course, a major activator of CaSR. This series of preliminary experiments was carried out to investigate the effect of different extracellular Ca2+ concentrations (1.2, 1.8, 2.5, 5 and 10 mm) on the capsaicin-evoked inward current. In the control conditions (without NPS 2143), the same capsaicin challenge (0.1 ��m, 4�C6 s) evoked a significantly smaller inward current with 2.5 mm Ca2+ and a significantly greater current with 10 mm Ca2+ in the ECS, when compared with the current amplitude recorded in our selleck inhibitor standard ECS with 1.8 mm Ca2+ included (P Resiquimod alter the ATP- or PBG-evoked inward current in the isolated rat vagal bronchopulmonary sensory neurons. Since the discovery of CaSR in bovine and human parathyroid glands, the concept has emerged that Ca2+ is an external ligand in addition to its well-documented role as an intracellular second messenger (Bouschet & Henley, 2005). Initial CaSR studies focused mainly on its key role in extracellular Ca2+ homeostasis, but recent accumulating evidence shows that CaSR is widely expressed in tissues with functions not directly related to plasma Ca2+ regulation, such as liver, heart, alimentary canal, lymphocytes, pancreas and the central and peripheral nervous systems (Ruat et al. 1995; Wang et al. 2003a; Bouschet & Henley, 2005; Ohsu et al. 2010; Magno et al. 2011). It has become apparent that CaSR regulates a variety of processes independent of systemic or local Ca2+ homeostasis (Brown & MacLeod, 2001; Magno et al. 2011).