Aminoglycoside antibiotics induce pH-sensitive activation of the calcium-sensing receptor

The aminoglycoside antibiotic (AGA) neomycin is a known agonist of the extracellular calcium-sensing receptor (CaR). To test whether other AGA drugs stimulate the CaR, we studied the relative effects of four AGAs on intracellular Ca 2+ concentration ([Ca 2+] i) using CaR-transfected human embryonic...

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Veröffentlicht in:	Biochemical and biophysical research communications 2002-09, Vol.297 (1), p.71-77
Hauptverfasser:	McLarnon, Stuart J, Holden, Darren, Ward, Donald T, Jones, Malcolm N, Elliott, Austin C, Riccardi, Daniela
Format:	Artikel
Sprache:	eng
Schlagworte:	Anti-Bacterial Agents - pharmacology Calcium receptor Cells, Cultured Fura-2 AM Humans Hydrogen-Ion Concentration Intracellular calcium Intracellular pH Low Density Lipoprotein Receptor-Related Protein-2 - biosynthesis Receptors, Calcium-Sensing Receptors, Cell Surface - agonists Receptors, Cell Surface - metabolism Tobramycin - pharmacology Transfection
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Zusammenfassung:	The aminoglycoside antibiotic (AGA) neomycin is a known agonist of the extracellular calcium-sensing receptor (CaR). To test whether other AGA drugs stimulate the CaR, we studied the relative effects of four AGAs on intracellular Ca 2+ concentration ([Ca 2+] i) using CaR-transfected human embryonic kidney (HEK)-293 cells. Gentamicin, tobramycin, and neomycin evoked dose-dependent increases in [Ca 2+] i with EC 50 values of 258, 177, and 43 μM, respectively, in CaR-transfected, but not in non-transfected cells. Kanamycin was ineffective at doses
ISSN:	0006-291X 1090-2104
DOI:	10.1016/S0006-291X(02)02133-2