Tetracyclines modulate cytosolic Ca2+ responses in the osteoclast associated with "Ca2+ receptor" activation.
We report the effects of tetracycline analogues on cytosolic Ca2+ transients resulting from application of ionic nickel (Ni2+), a potent surrogate agonist of the osteoclast Ca2+ "receptor". Preincubation with minocycline (1 mg/l) or a chemically modified tetracycline, 4-dedimethyl-aminotetracycline (CMT-1) (1 or 10 mg/l), resulted in a significant attenuation of the magnitude of the cytosolic [Ca2+] response to an application of 5 mM-[Ni2+]. Preincubation with doxycycline (1 or 10 mg/l) failed to produce similar results. In addition, application of minocycline alone (0.1-100 mg/l) resulted in a 3.5-fold elevation of cytosolic [Ca2+]. The results suggest a novel action of tetracyclines on the osteoclast Ca2+ "receptor".
Bax
C M
CM
Division of Biochemical Medicine, St. George's Hospital Medical School, London, UK.
Shankar
V S
VS
Towhidul Alam
A S
AS
Bax
B E
BE
Moonga
B S
BS
Huang
C L
CL
Zaidi
M
M
Rifkin
B R
BR
D000818:Animals; D002118:Calcium / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D003600:Cytosol / Q000737:chemistry* / Q000502:physiology; D004318:Doxycycline / Q000494:pharmacology; D008911:Minocycline / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D010010:Osteoclasts / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis* / Q000378:metabolism / Q000502:physiology*; D013752:Tetracycline / Q000494:pharmacology*
D018160:Receptors, Cytoplasmic and Nuclear; C053450:4-des-dimethylaminotetracycline; D009532:Nickel; D013752:Tetracycline; D008911:Minocycline; D004318:Doxycycline; D002118:Calcium