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 o steoblast-like cells enhances the proliferation and differentiation of thes e cells. In the present study, we investigated the effect of epinephrine, a n agonist of Gi-protein-coupled receptors in MC3T3-E1 cells, on Pi transpor t, type III Pi transporter expression, and the signaling mechanism(s) invol ved in this response. Epinephrine time- and dose-dependently stimulated sod ium-dependent Pi transport and this effect was dependent on RNA and protein synthesis. This effect was associated with a related time-dependent increa se in Pit-1 mRNA expression. Kinetic analysis indicated that the change in Pi transport activity induced by epinephrine was due to alteration in the m aximal rate of Pi transport. Investigation of Pi transport stimulation by s everal adrenergic agonists and its inhibition by spiperone suggest that the effect of epinephrine on Pi transport was mediated by alpha1-adrenergic re ceptors, Pertussis toxin, which inactivates Gi/o proteins, significantly bl unted the stimulatory effect of epinephrine on Pi transport, Analysis of th e signaling pathways involved in this response has suggested a major role o f protein kinase C and a small contribution from the mitogen-activated prot ein kinase Erk (MAPK(erk)). The results show that, in MC3T3-E1 osteoblast-l ike 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 tra nsporters, (C) 2001 by Elsevier Science Inc. All rights reserved.