Substance p regulates the function of rabbit cultured osteoclast; Increase of intracellular free calcium concentration and enhancement of bone resorption

The effects of substance P on cultured rabbit osteoclasts were investigated. The intracellular Ca2+ concentration ([Ca2+](i)) which was monitored by the microfluorometric technique using fura-2, in osteoclasts elevated by the addition of substance P (0.3-5 mu M) The EC50 value of substance P was about 200 nM. This substance P-evoked [Ca2+](i) elevation was not observed in the Ca2+ -free medium. Simultaneous application of spantide, a substance P receptor antagonist, blocked the Ca2+ response. The addition of substance P (0.1-10 mu M) to cultured osteoclasts enhanced their bone resorption activity which was evaluated by the pit formation assay. Maximum enhancement of the pit formation by substance P (5 mu M) peaked at about 170% of the control level. The addition of substance P receptor antagonists also inhibited the enhancement of the bone resorption by substance P addition. Substance P possibly stimulates the bone remodeling by osteoclasts via the [Ca2+](i) elevation, (C) 1999 Academic Press.