Q. Gu: Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31207, USA.
Exp Physiol. 2013 Nov;98(11):1631-42. doi: 10.1113/expphysiol.2013.074633. Epub 2013 Aug 2.
Extracellular calcium-sensing receptor (CaSR) has been known to play a critical role in the maintainance of systemic Ca(2+) homeostasis. Recent studies have shown that CaSR is also expressed in many tissues that are not directly related to plasma Ca(2+) regulation, such as the central and peripheral nervous system, where the function of this receptor remains to be defined. In this study, we aimed to investigate the expression of CaSR and its potential interaction with transient receptor potential vanilloid receptor type 1 (TRPV1) in rat vagal bronchopulmonary sensory neurons. Our immunohistochemical experiments demonstrated the expression of CaSR in these sensory neurons as well as in trachea and lung parenchyma. Results from our whole-cell patch-clamp recordings in isolated neurons showed that strong activation of CaSR with high concentrations of its agonists, including spermine, NPS R-568 and Ca(2+), inhibited the capsaicin-evoked whole-cell inward current. Blockade of CaSR with its antagonists NPS 2390 and NPS 2143 significantly enhanced the capsaicin-evoked TRPV1 current. These data suggest that CaSR is likely to be involved in the integration of primary bronchopulmonary sensory inputs in physiological and/or pathophysiological conditions.
细胞外钙敏感受体 (CaSR) 在维持全身钙稳态中起着关键作用。最近的研究表明，CaSR 也在许多与血浆 Ca(2+) 调节不直接相关的组织中表达，如中枢和外周神经系统，其受体功能仍有待确定。在这项研究中，我们旨在研究 CaSR 的表达及其在大鼠迷走性支气管肺感觉神经元中与瞬时受体电位香草酸受体 1 (TRPV1) 的潜在相互作用。我们的免疫组织化学实验表明 CaSR 在这些感觉神经元以及气管和肺实质中表达。我们在分离神经元中的全细胞膜片钳记录结果表明，高浓度 CaSR 激动剂，包括亚精胺、NPS R-568 和 Ca(2+)，强烈激活 CaSR，抑制辣椒素诱发的全细胞内向电流。CaSR 的拮抗剂 NPS 2390 和 NPS 2143 阻断显著增强了辣椒素诱发的 TRPV1 电流。这些数据表明，CaSR 可能参与生理和/或病理生理条件下原发性支气管肺感觉传入的整合。
