Characterization of Ca2+-Sensing Receptor-Mediated Ca2+Influx in Microvascular bEND.3 Endothelial Cells

Iat Lon Leong, Tien Yao Tsai, Lian Ru Shiao, Yu Mei Zhang, Kar Lok Wong, Paul Chan, Yuk Man Leung

Research output: Contribution to journalArticlepeer-review

Abstract

Ca2+-sensing receptors (CaSR), activated by elevated concentrations of extracellular Ca2+, have been known to regulate functions of thyroid cells, neurons, and endothelial cells (EC). In this report, we studied CaSR-mediated Ca2+influx in mouse cerebral microvascular EC (bEND.3 cells). Cytosolic free Ca2+concentration and Mn2+influx were measured by fura-2 microfluorometry. High (3 mM) Ca2+(CaSR agonist), 3 mM spermine (CaSR agonist), and 10 μM cinacalcet (positive allosteric modulator of CaSR) all triggered Ca2+influx; however, spermine, unlike high Ca2+and cinacalcet, did not promote Mn2+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 Ca2+influx triggered by cinacalcet and high Ca2+but not by spermine. Ca2+influx triggered by high Ca2+, spermine, and cinacalcet was similarly suppressed by A784168, a potent and selective TRPV1 antagonist. Our results suggest that CaSR activation triggered Ca2+influx via TRPV1 channels; intriguingly, pharmacological, and permeability properties of such Ca2+influx depended on the stimulating ligands.

Original languageEnglish
Pages (from-to)80-87
Number of pages8
JournalChinese Journal of Physiology
Volume64
Issue number2
DOIs
Publication statusPublished - Mar 1 2021

Keywords

  • Ca
  • Ca-sensing receptors
  • endothelium
  • spermine
  • TRP channels

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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