title: Calcium-sensing receptor in rat vagal bronchopulmonary sensory neurons regulates the function of the capsaicin receptor TRPV1.
abstract: 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.
authors.affiliation: Q. Gu: Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31207, USA. gu_q@mercer.edu.
authors.forename: Qihai
authors.initials: Q
authors.lastname: Gu
authors.forename: Zhanna V
authors.initials: ZV
authors.lastname: Vysotskaya
authors.forename: Charles R
authors.initials: CR
authors.lastname: Moss
authors.forename: Martin K
authors.initials: MK
authors.lastname: Kagira
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Gilbert
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010627:Phenethylamines; D011437:Propylamines; D011810:Quinoxalines; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013096:Spermine / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000502:physiology
chemical_list: C569355:2-quinoxaline-carboxamide-N-adamantan-1-yl; D000814:Aniline Compounds; D001645:Biguanides; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010627:Phenethylamines; D011437:Propylamines; D011810:Quinoxalines; D044169:Receptors, Calcium-Sensing; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D013096:Spermine; D000255:Adenosine Triphosphate; D000218:Adamantane; D002211:Capsaicin; D002118:Calcium; C008846:phenyl biguanide