Effect of the phosphodiesterase 4 inhibitor, rolipram, on retinoic acid-increased alkaline phosphatase activity in the mouse fibroblastic C3H10T1/2 cell line.
We have evaluated effects of a phosphodiesterase (PDE) 4 inhibitor on retinoic acid-increased alkaline phosphatase activity in the mouse fibroblastic C3H10T1/2 clone 8 (10T1/2) cell line. 10T1/2 cells were cultured in minimum essential medium (MEM) and 10% fetal bovine serum with or without 1 microM retinoic acid and/or the PDE 4 inhibitor, rolipram, and harvested at specific intervals before measurement of alkaline phosphatase activity, cAMP production in response to parathyroid hormone, osteocalcin synthesis and expression, and phosphodiesterase activity. Retinoic acid-increased alkaline phosphatase activity, and slightly enhanced cAMP production in response to parathyroid hormone. However, it did not affect osteocalcin synthesis and expression. In the presence of retinoic acid, PDE 4 activity was not changed. A PDE 4 inhibitor, rolipram, and cAMP analog, 8-bromo-cAMP dramatically increased retinoic acid's ability to induce alkaline phosphatase activity. This is the first report that PDE 4 may be involved in regulation of retinoic acid-increased alkaline phosphatase activity.
Murata
Taku
T
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu, 514-8507, Mie, Japan. muratat@clin.medic.mie-u.ac.jp <muratat@clin.medic.mie-u.ac.jp>
Sugatani
Toshifumi
T
Shimizu
Kasumi
K
Manganiello
Vincent C
VC
Tagawa
Toshiro
T
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D000469:Alkaline Phosphatase / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics; D010281:Parathyroid Hormone / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D020889:Rolipram / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
D010281:Parathyroid Hormone; D010726:Phosphodiesterase Inhibitors; D015675:Osteocalcin; D014212:Tretinoin; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram