Stimulatory effect of endothelin-1 on Na-dependent phosphate transport and its signaling mechanism in osteoblast-like cells
✍ Scribed by Hiroko Masukawa; Yoshitaka Miura; Ikuko Sato; Yutaka Oiso; Atsushi Suzuki
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 172 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0730-2312
- DOI
- 10.1002/jcb.1206
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✦ Synopsis
Abstract
Endothelin‐1 (ET‐1) has been reported to modulate bone metabolism both in vivo and in vitro. In the present study, we investigated the effect of ET‐1 on inorganic phosphate (Pi) transport in osteoblast‐like cells, which is now considered to be important for the initiation of bone matrix calcification. ET‐1 time‐ and dose‐dependently stimulated Na‐dependent Pi transport in mouse calvaria‐derived osteoblast‐like MC3T3‐E1 cells, and this effect was dependent on transcriptional and translational process. Kinetic analysis indicated that the change in Pi transport activity induced by ET‐1 was due to alteration in the number of the Pi transporter. BQ123, a selective antagonist for ET~A~ receptor, suppressed the ET‐1‐induced Pi transport, but BQ788, a selective antagonist for ET~B~ receptor, had no effect. The inhibition of phosphoinositide hydrolysis by phospholipase C (PLC) partially attenuated the Pi transport by ET‐1. Propranolol, which inhibits phosphatidic acid phosphohydrolase, also suppressed ET‐1‐induced Pi transport. On the contrary, indomethacin did not affect the stimulatory effect of Pi transport by ET‐1. Calphostin C, a protein kinase C (PKC) inhibitor, significantly blunted the stimulatory effect of ET‐1 on Pi transport. Combined effect of PMA and ET‐1 on Pi transport was not additive. Pi transport induced by ET‐1 was also suppressed in PKC down‐regulated cells. In conclusion, the results of the present study indicate that in MC3T3‐E1 osteoblast‐like cells, ET‐1 acting through ET receptor links to a stimulation of Pi transport via activation of PKC through both phosphoinositide and phosphatidylcholine hydrolyses. © 2001 Wiley‐Liss, Inc.