Dissociation between parathyroid hormone‐stimulated cAMP and calcium increase in UMR‐106‐01 cells

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Abstract
We used the osteogenic sarcoma cell line, UMR-106-01, to determine whether the rise in free cytosolic Ca2+ concentration ([Ca2+]i) and cellular cAMP following PTH stimulation are able to be regulated independently. For this purpose, we compared the effect of a PTH antagonist, stimulation of protein kinase C, augmentation by prostaglandins, and the time course of desensitization of the two cellular responses. Two × 10−7 M of the PTH antagonist 8,18Nle 34Tyr-bPTH(3–34) amide ([Nle, Tyr]bPTH(3–34)A) was required to inhibit 10−9 M bPTH(1–34)-stimulated cAMP generation by 50%. 10−7 M bPTH(1–34) completely overcame the inhibition induced by 10−6 M [Nle, Tyr]bPTH(3–34)A. Only 7 × 10−8 M and 2.7 × 10−7 M [Nle, Tyr]bPTH(3–34)A were required to half maximally inhibit the [Ca2+]i increase evoked by 3 × 10−8 and 10−7 M bPTH(1–34), respectively. In addition, dissociation between [Ca2+]i and cAMP signals was observed when modulation by protein kinase C and prostaglandins was tested. Preincubation of the cells with 10 nM TPA for 5 minutes markedly inhibited the PTH-evoked [Ca2+]i increase. Short incubation with PGF2α augmented the PTH-evoked [Ca2+]i increase. Similar pretreatments had no effect on the PTH-stimulated cAMP increase. Finally, preincubation with 1.5 × 10−9 M bPTH(1–34) for 20 minutes almost completely blocked the effect of 10−7 M bPTH(1–34) on [Ca2+]i, while preincubation with 5 × 10−9 M bPTH(1–34) for 4 hours was required to inhibit the effect of 10−8 M bPTH(1–34) on cAMP production by 50%. The differences in the regulation of the two PTH-stimulated cellular signaling systems, in particular, the response to antagonists and the time course of desensitization, could be at the level of the PTH receptor(s) or at a postreceptor domain.

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