Inhibitory effect of okadaic acid on bone resorption in neonatal mouse calvaria in vitro. Protein dephosphorylation as an important regulatory mechanism in the bone resorption process.
Okadaic acid (OA), a potent inhibitor of protein phosphatase type 1 and protein phosphatase type 2A was studied for its effect on bone resorption in neonatal mouse calvaria. OA (0.01 to 1000 ng/ml) had no effect on the basal bone resorption rate, except at 1000 ng/ml, were a small inhibitory effect was observed. Resorption stimulated by parathyroid hormone (10(-8) M) was abolished in the presence of OA, half maximal inhibition being observed at 1 ng/ml. However, at 50 ng/ml or higher, OA significantly increased lactate dehydrogenase activity in the medium, indicating a cytotoxic effect at these concentrations. Similar inhibitory effects were observed when bone resorption was stimulated by 1,25-dihydroxycholecalciferol (10(-8) M) or prostaglandin E2 (10(-6) M). From this it is concluded that protein dephosphorylation may represent an important regulatory mechanism in the bone resorption process.
Feyen
J H
JH
Sandoz Pharma Ltd, Preclinical Research, CH-4002 Basel, Switzerland.
Kuntzelmann
G M
GM
D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D002117:Calcitriol / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D019319:Okadaic Acid; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*
D004988:Ethers, Cyclic; D010281:Parathyroid Hormone; D019319:Okadaic Acid; D007770:L-Lactate Dehydrogenase; D010749:Phosphoprotein Phosphatases; D002117:Calcitriol; D015232:Dinoprostone