Open AccessCharacterization of Ca2+ -Sensing Receptor-Mediated Ca2+ Influx in Microvascular bEND.3 Endothelial Cells
Author(s) -
Iat-Lon Leong,
TienYao Tsai,
LianRu Shiao,
Yumei Zhang,
KarLok Wong,
Paul Chan,
YukMan Leung
Publication year - 2021
Publication title -
chinese journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.396
H-Index - 31
eISSN - 2666-0059
pISSN - 0304-4920
DOI - 10.4103/cjp.cjp_93_20
Subject(s) - spermine , cinacalcet , chemistry , ruthenium red , agonist , biophysics , extracellular , channel blocker , allosteric regulation , receptor , calcium sensing receptor , calcium , endocrinology , medicine , biochemistry , calcium metabolism , biology , parathyroid hormone , organic chemistry , secondary hyperparathyroidism , enzyme
Ca 2+ -sensing receptors (CaSR), activated by elevated concentrations of extracellular Ca 2+ , have been known to regulate functions of thyroid cells, neurons, and endothelial cells (EC). In this report, we studied CaSR-mediated Ca 2+ influx in mouse cerebral microvascular EC (bEND.3 cells). Cytosolic free Ca 2+ concentration and Mn 2+ influx were measured by fura-2 microfluorometry. High (3 mM) Ca 2+ (CaSR agonist), 3 mM spermine (CaSR agonist), and 10 μM cinacalcet (positive allosteric modulator of CaSR) all triggered Ca 2+ influx; however, spermine, unlike high Ca 2+ and cinacalcet, did not promote Mn 2+ influx and its response was poorly sensitive to SKF 96365, a TRP channel blocker. Consistently, 2-aminoethoxydiphenyl borate and ruthenium red (two other general TRP channel blockers) suppressed Ca 2+ influx triggered by cinacalcet and high Ca 2+ but not by spermine. Ca 2+ influx triggered by high Ca 2+ , spermine, and cinacalcet was similarly suppressed by A784168, a potent and selective TRPV1 antagonist. Our results suggest that CaSR activation triggered Ca 2+ influx via TRPV1 channels; intriguingly, pharmacological, and permeability properties of such Ca 2+ influx depended on the stimulating ligands.