Effects of human PTH-related peptide and human PTH on cyclic AMP production and cytosolic free calcium in an osteoblastic cell clone.
Recently, human parathyroid hormone-related peptide (hPTHrP) has been purified and its amino acid sequence determined. Within the amino-terminal 13 residues of hPTHrP, 8 amino acids were found homologous between hPTHrP and human PTH (hPTH). This peptide was reported to stimulate cyclic AMP (cAMP) production in osteoblastic cell lines (UMR106 and ROS17/2.8). However, whether or not this peptide affects another second messenger, i.e., cytosolic free calcium ([Ca2+]i), in osteoblasts has not yet been determined. Therefore, in the present study, we examined the effects of synthetic amino-terminal fragments of hPTHrP (Tyr40hPTHrP1-40 and hPTHrP1-34) on intracellular cAMP production and [Ca2+]i in an osteoblastic cell line (MC3T3-E1) and compared them with those of hPTH1-34. Human PTHrP1-34, Tyr40hPTHrP1-40 and hPTH1-34 stimulated cAMP production in an equipotent manner at concentrations ranging from 2.5 x 10(-10) to 1.3 x 10(-6) M. Human PTH1-34 at concentrations from 2.5 x 10(-7) to 1.3 x 10(-6) M significantly (P less than 0.05) increased [Ca2+]i, but hPTHrP1-34 and Tyr40hPTHrP1-40 at the same concentrations did not. These results suggest a different receptor-mediated mechanism for [Ca2+]i increase between hPTHrP and hPTH, although these two peptides appear to share the same receptor site(s) which is coupled to the cAMP system in MC3T3-E1.
Yamada
H
H
Department of Medicine, Kobe University School of Medicine, Japan.
Tsutsumi
M
M
Fukase
M
M
Fujimori
A
A
Yamamoto
Y
Y
Miyauchi
A
A
Fujii
Y
Y
Noda
T
T
Fujii
N
N
Fujita
T
T
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000032:analysis; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000494:pharmacology*; D010006:Osteoblasts / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins; D019379:Teriparatide
D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D019379:Teriparatide; C060519:parathyroid hormone-related protein (1-40), Tyr(40)-; D000242:Cyclic AMP; D002118:Calcium