Stimulation of sodium-dependent inorganic phosphate transport by activation of Gi/o-protein-coupled receptors by epinephrine in MC3T3-E1 osteoblast-like cells

Recent data have shown that activation of Gi-protein-coupled receptors in osteoblast-like cells enhances the proliferation and differentiation of these cells. In the present study, we investigated the effect of epinephrine, an agonist of Gi-protein-coupled receptors in MC3T3-E1 cells, on Pi transport, type III Pi transporter expression, and the signaling mechanism(s) involved in this response. Epinephrine time- and dose-dependently stimulated sodium-dependent Pi transport and this effect was dependent on RNA and protein synthesis. This effect was associated with a related time-dependent increase in Pit-1 mRNA expression. Kinetic analysis indicated that the change in Pi transport activity induced by epinephrine was due to alteration in the maximal rate of Pi transport. Investigation of Pi transport stimulation by several adrenergic agonists and its inhibition by spiperone suggest that the effect of epinephrine on Pi transport was mediated by alpha1-adrenergic receptors, Pertussis toxin, which inactivates Gi/o proteins, significantly blunted the stimulatory effect of epinephrine on Pi transport, Analysis of the signaling pathways involved in this response has suggested a major role of protein kinase C and a small contribution from the mitogen-activated protein kinase Erk (MAPK(erk)). The results show that, in MC3T3-E1 osteoblast-like cells, activation of Gi/o-protein-coupled receptors induces stimulation of Pi transport. This effect is mediated by activation of protein kinase C and the MAPK(erk) pathway and probably involves the synthesis of Pit-1 transporters, (C) 2001 by Elsevier Science Inc. All rights reserved.