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Calcium‐sensing receptor in rat vagal bronchopulmonary sensory neurons regulates the function of the capsaicin receptor TRPV1
Author(s) -
Gu Qihai,
Vysotskaya Zhanna V.,
Moss II Charles R.,
Kagira Martin K.,
Gilbert Carolyn A.
Publication year - 2013
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2013.074633
Subject(s) - trpv1 , capsaicin , calcium sensing receptor , receptor , endocrinology , medicine , extracellular , sensory system , transient receptor potential channel , calcium imaging , sensory nerve , agonist , chemistry , calcium , neuroscience , biology , microbiology and biotechnology , calcium metabolism
New findings• What is the central question of this study? Extracellular calcium‐sensing receptor (CaSR) is known to play a critical role in the maintainance of systemic calcium homeostasis. Recent studies suggest that CaSR is also involved in many biological processes unrelated to Ca 2+ balance. However, the expression of CaSR and its potential interaction with transient receptor potential vanilloid receptor type 1 (TRPV1) function in bronchopulmonary afferent nerves is not known. • What is the main finding and its importance? Our immunohistochemical study demonstrated the expression of CaSR in bronchopulmonary sensory neurons. Our patch‐clamp recordings showed that strong activation of CaSR inhibits, whereas reduced CaSR function potentiates, the capsaicin‐evoked TRPV1 current in these neurons. Our data suggest that CaSR plays an integrative role in bronchopulmonary afferent signalling.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.