Additive effects of parathyroid hormone and calcitonin on adenosine 3',5'-monophosphate release in newly established perfusion system of rat femur

A new perfusion system of isolated rat femora was established, and the effect of PTH or calcitonin (CT) on cAMP release from the adult bone was examined. Stimulation of cAMP release from the isolated perfused bone peaked rapidly between 5 and 10 min after human PTH (hPTH)-(1-34) or eel CT injection, respectively, and declined gradually toward the preinjection level. However CT exhibited a longer lived effect than PTH. Release of cAMP was still significantly greater than control at 60 min after a bolus injection of CT. The rate of cAMP release was directly related to the dose of PTH or CT. H2O2-oxidized PTH (biologically inactive) caused no increase in cAMP release. hPTH-(1-34) was markedly more potent than hPTH-(1-84) in stimulating cAMP release from the perfused bone on an equimolar basis. Simultaneous administration of 5 micrograms PTH and 5 micrograms CT at maximal stimulatory doses produced additive effects, indicating the presence of separate receptor sites for PTH and CT in the bone. In conclusion, this system provides us a means by which hormone actions on adult bone with integrity of the organ can be evaluated and therefore makes possible systemic investigation of the osteoblast-osteoclast function.