TETRACYCLINES MODULATE CYTOSOLIC CA2+ RESPONSES IN THE OSTEOCLAST ASSOCIATED WITH CA2+ RECEPTOR ACTIVATION

We report the effects of tetracycline analogues on cytosolic Ca2+ tran sients resulting from application of ionic nickel (Ni2+), a potent sur rogate agonist of the osteoclast Ca2+ ''receptor''. Preincubation with minocycline (1 mg/1) or a chemically modified tetracycline, 4-dedimet hyl-aminotetracycline (CMT-1) (1 or 10 mg/1), resulted in a significan t attenuation of the magnitude of the CytoSoliC [Ca2+] response to an application of 5 mM-[Ni2+]. Preincubation with doxycycline (1 or 10 mg /1) failed to produce similar results. In addition, application of min ocycline alone (0.1-100 mg/l) resulted in a 3.5-fold elevation of cyto solic [Ca2+]. The results suggest a novel action of tetracyclines on t he osteoclast Ca2+ ''receptor''.