| Abstract: | We studied the cAMP response of cultured rat calvaria to parathyroid hormone (PTH) and prostaglandins (PG) in order to test the hypothesis that PTH action is mediated by PG. PTH and PGE1 each caused an 8-fold increase in tissue cAMP during 15 min incubation. There was an additive response to the combination of the two agonists at maximally effective individual concentrations. Similar results were obtained when adenylate cyclase activity in bone homogenates were measured. Calvaria incubated for 60 min with PGE1 were desensitized to further stimulation by PGE1, but responded normally to PTH. Indomethacin, aspirin and phenylbutazone, 10(-5)M, had no effect on the cAMP response to PTH. At millimolar concentration these agents did block the hormone response; however, the response to exogenous PGE1 and the fluoride-sensitive adenylate cyclase were also inhibited. Thus, it appears that the effects of high concentrations of the anti-inflammatory drugs on cAMP formation are non-specific. Our results suggest that receptors in bone for PTH and prostaglandins are separate and independent, and that the cAMP response to PTH is not mediated by prostaglandins. |
