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 (pH(i)), 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 pH(i) by means of an amiloride-inhibitable Na⁺-H⁺ exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pH(i) with a half-maximal effect at 10^-11 M. At 1 h, the maximal depression of pH(i) was 0.1 ± 0.01 U. This effect was reproduced by forskolin, but neither agent influenced pH(i) in the presence of amiloride. Incorporation of [³H]thymidine was reduced by rPTH (half-maximal dose ~10^-11 M), forskolin, and N⁶,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pH(i) 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 pH(i) in these circumstances. It is concluded that PTH decreases pH(i) and growth in UMR 106 cells but that these changes can be dissociated. Depression of pH(i) 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.