Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells.
It has recently become apparent that a number of hormones and growth factors modulate cytosolic pH (pHi), and there is some evidence that this in turn may influence cell growth. We have examined the effects of parathyroid hormone (PTH) on both these parameters in an osteoblast-like cell line, UMR 106. Preliminary studies, using the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein indicated that these cells regulate pHi by means of an amiloride-inhibitable Na+-H+ exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pHi with a half-maximal effect at 10(-11) M. At 1 h, the maximal depression of pHi was 0.1 +/- 0.01 U. This effect was reproduced by forskolin, but neither agent influenced pHi in the presence of amiloride. Incorporation of [3H]thymidine was reduced by rPTH (half-maximal dose approximately 10(-11) M), forskolin, and N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pHi and [3H]thymidine incorporation, and amiloride reduced both indexes. However, rPTH remained a potent inhibitor of [3H]thymidine incorporation in the presence of amiloride, even though it did not affect pHi in these circumstances. It is concluded that PTH decreases pHi and growth in UMR 106 cells but that these changes can be dissociated. Depression of pHi may have other important effects on bone metabolism, such as reducing cell-cell communication, and may be associated with alkalinization of the bone fluid compartment.
Reid
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Metabolism Division, Jewish Hospital of St. Louis, Missouri 63110.
Civitelli
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Avioli
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Hruska
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D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D010006:Osteoblasts / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D002352:Carrier Proteins; D010281:Parathyroid Hormone; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine