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 Ca(2+) concentration ([Ca(2+)](i)) which was monitored by the microfluorometric technique using fura-2, in osteoclasts elevated by the addition of substance P (0.3-5 microM). The EC(50) value of substance P was about 200 nM. This substance P-evoked [Ca(2+)](i) elevation was not observed in the Ca(2+)-free medium. Simultaneous application of spantide, a substance P receptor antagonist, blocked the Ca(2+) response. The addition of substance P (0.1-10 microM) 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 microM) 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 [Ca(2+)](i) elevation.
Mori
T
T
School of Medicine, Ehime University, Ehime, Shigenobu, 791-0295, Japan.
Ogata
T
T
Okumura
H
H
Shibata
T
T
Nakamura
Y
Y
Kataoka
K
K
D000704:Analysis of Variance; D000818:Animals; D001681:Biological Assay; D001713:Biphenyl Compounds / Q000494:pharmacology; D001862:Bone Resorption / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D011817:Rabbits; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001713:Biphenyl Compounds; D013373:Substance P; C042867:spantide; D002118:Calcium; C066892:CP 96345