ET(A) receptor mediates the signaling of endothelin-1 in osteoblast-like cells

Atsushi Suzuki, J. Shinoda, Y. Watanabe-Tomita, N. Ozaki, Y. Oiso, Osamu Kozawa

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

We previously reported that endothelin-1 (ET-1) stimulates phosphatidylcholine-hydrolyzing phospholipase D independently of phosphoinositide hgdrolysis in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the characteristics of the receptors mediating ET-1-induced intracellular signaling pathway in MC3T3-E1 cells. Cyclo-D-Trp-D-Asp-Pro-D-Val-Leu (BQ123), a selective ET(A) receptor antagonist, significantly inhibited the ET-1-induced formation of inositol phosphates in a dose-dependent manner in the range between 22 nmol/L (IC50) and 2.2 μmol/L (IC50 x 100). On the contrary, N-cis-2,6- dimethylpiperidinocarbonyl-L-γMeLeu-D-Trp(COOMe)-D-Nle-ONa (BQ788), a selective ET(B) receptor antagonist, had no effect on the ET-1-induced formation of inositol phosphates in the range between 1.2 nmol/L (IC50) and 120 nmol/L (IC50 x 100), BQ123 significantly suppressed the ET-1-induced formation of choline dose-dependently, however, BQ788 did not affect the choline formation, BQ123 also inhibited the ET-1-induced release of arachidonic acid, but BQ788 had little effect. The results strongly suggest that ET(A) receptor mediates the three intracellular signaling pathways of ET-1: (1) phosphoinositide hydrolysis by phospholipase C; (2) phosphatidylcholine hydrolysis by phospholipase D; and (3) arachidonic acid release in osteoblast-like cells.

Original languageEnglish
Pages (from-to)143-146
Number of pages4
JournalBone
Volume21
Issue number2
DOIs
Publication statusPublished - 01-08-1997
Externally publishedYes

Fingerprint

Endothelin-1
Osteoblasts
Inhibitory Concentration 50
Phospholipase D
Inositol Phosphates
Choline
Phosphatidylcholines
Arachidonic Acid
Hydrolysis
Phosphoinositide Phospholipase C
Endothelin A Receptors
Phosphatidylinositols
cyclo(Trp-Asp-Pro-Val-Leu)
BQ 788

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Suzuki, A., Shinoda, J., Watanabe-Tomita, Y., Ozaki, N., Oiso, Y., & Kozawa, O. (1997). ET(A) receptor mediates the signaling of endothelin-1 in osteoblast-like cells. Bone, 21(2), 143-146. https://doi.org/10.1016/S8756-3282(97)00096-3
Suzuki, Atsushi ; Shinoda, J. ; Watanabe-Tomita, Y. ; Ozaki, N. ; Oiso, Y. ; Kozawa, Osamu. / ET(A) receptor mediates the signaling of endothelin-1 in osteoblast-like cells. In: Bone. 1997 ; Vol. 21, No. 2. pp. 143-146.
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Suzuki, A, Shinoda, J, Watanabe-Tomita, Y, Ozaki, N, Oiso, Y & Kozawa, O 1997, 'ET(A) receptor mediates the signaling of endothelin-1 in osteoblast-like cells', Bone, vol. 21, no. 2, pp. 143-146. https://doi.org/10.1016/S8756-3282(97)00096-3

ET(A) receptor mediates the signaling of endothelin-1 in osteoblast-like cells. / Suzuki, Atsushi; Shinoda, J.; Watanabe-Tomita, Y.; Ozaki, N.; Oiso, Y.; Kozawa, Osamu.

In: Bone, Vol. 21, No. 2, 01.08.1997, p. 143-146.

Research output: Contribution to journalArticle

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T1 - ET(A) receptor mediates the signaling of endothelin-1 in osteoblast-like cells

AU - Suzuki, Atsushi

AU - Shinoda, J.

AU - Watanabe-Tomita, Y.

AU - Ozaki, N.

AU - Oiso, Y.

AU - Kozawa, Osamu

PY - 1997/8/1

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N2 - We previously reported that endothelin-1 (ET-1) stimulates phosphatidylcholine-hydrolyzing phospholipase D independently of phosphoinositide hgdrolysis in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the characteristics of the receptors mediating ET-1-induced intracellular signaling pathway in MC3T3-E1 cells. Cyclo-D-Trp-D-Asp-Pro-D-Val-Leu (BQ123), a selective ET(A) receptor antagonist, significantly inhibited the ET-1-induced formation of inositol phosphates in a dose-dependent manner in the range between 22 nmol/L (IC50) and 2.2 μmol/L (IC50 x 100). On the contrary, N-cis-2,6- dimethylpiperidinocarbonyl-L-γMeLeu-D-Trp(COOMe)-D-Nle-ONa (BQ788), a selective ET(B) receptor antagonist, had no effect on the ET-1-induced formation of inositol phosphates in the range between 1.2 nmol/L (IC50) and 120 nmol/L (IC50 x 100), BQ123 significantly suppressed the ET-1-induced formation of choline dose-dependently, however, BQ788 did not affect the choline formation, BQ123 also inhibited the ET-1-induced release of arachidonic acid, but BQ788 had little effect. The results strongly suggest that ET(A) receptor mediates the three intracellular signaling pathways of ET-1: (1) phosphoinositide hydrolysis by phospholipase C; (2) phosphatidylcholine hydrolysis by phospholipase D; and (3) arachidonic acid release in osteoblast-like cells.

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