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 μM). The EC50value of substance P was about 200 nM. This substance P-evoked [Ca2+]ielevation 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 μM) 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 μM) 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+]ielevation.