Role of phosphodiesterase in the parathormone-stimulated adenosine 3',5'-monophosphate response in bone cell populations enriched in osteoclasts and osteoblasts.
The stimulation of cAMP formation by parathormone was assessed in isolated bone cell populations enriched in either osteoclast-like (CL) or osteoblast-like (BL) cells. In the presence of the potent phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), at 37 C, the CL cells produced at least 20% the amount of cAMP formed by the BL cells, but only about 5% when the inhibitor was omitted. The rate of cAMP production in response to parathormone was measured at 23 C in order to obtain a better indication of the capacity of the cells to generate this nucleotide. Under these conditions, the CL cells produced cAMP at a rate of 50-60% that of the BL cells regardless of whether IBMX was present. The phosphodiesterase activity in CL cell extracts was twice that in BL cell extracts, and IBMX inhibited this activity. These results show that when an effective inhibitor of phosphodiesterase is present, the CL cells exhibit a significant response to parathormone in terms of cAMP production. The possibility that the cAMP response in the CL cells was due to contaminating BL cells (which would have to be about 50% of the total cell number) was ruled out by the demonstration that citrate decarboxylating activity, a marker for the BL cells, was low and was not inhibited by parathormone. These data reinforce the earlier contention that parathormone directly stimulates adenylate cyclase in both osteoclasts and osteoblasts and activates bone resorption via cAMP as second messenger.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*
D010281:Parathyroid Hormone; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015056:1-Methyl-3-isobutylxanthine