The effects of the endothelin family peptides on cultured osteoblastic cells from rat calvariae.
The activities of three isoforms of the endothelin (ET) family peptides, ET-1, ET-2 and ET-3, were studied in cultured osteoblastic cells from neonatal rat calvariae. All three isoforms induce stimulation of DNA synthesis and reductions in cellular alkaline phosphatase activity in a dose-dependent manner with the rank order of potency: ET-1 congruent to ET-2 greater than ET-3. The 125I-labeled ET binding and affinity-cross linking experiments show the presence of a single class of the ET binding sites with a more than 10-fold higher affinity for ET-1 and ET-2 as compared to ET-3. The endothelins dose-dependently stimulate the production of inositol phosphates and induce mobilization of Ca2+ with the similar relative potency to that for the receptor binding. These results indicate that osteoblastic cells possess the endothelin receptor with a high affinity for ET-1 and ET-2 that is coupled to phospholipase C, and that the endothelins modulate cellular functions via this receptor.
Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
Y
Y
Takuwa
T
T
Masaki
K
K
Yamashita
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects*; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D016232:Endothelins; D007295:Inositol Phosphates; D010455:Peptides; D004247:DNA; D000469:Alkaline Phosphatase; D002118:Calcium