Prostacyclin IP receptor up-regulates the early expression of C/EBP beta and C/EBP delta in preadipose cells

Prostacyclin (PGI(2)) and its stable analogue carbacyclin (cPGI(2)) are kno wn to trigger the protein kinase A pathway after binding to the cell surfac e IP receptor and to promote or enhance terminal differentiation of adipose precursor cells to adipose cells. The early expression of C/EBP beta and C /EBP beta is known to be critical for adipocyte differentiation in vitro as well as in vivo. We report herein that in Ob1771 and 3T3-F442A preadipose cells, activation of the IP receptor by specific agonists (PGI(2), cPGI(2) and BMY 45778) is sufficient to up-regulate rapidly the expression of C/EBP beta and C/EBP delta. Cyclic AMP-elevating agents are able to substitute f or IP receptor agonists, in agreement with the coupling of IP receptor to a denylate cyclase. Consistent with the fact that PGI(2) is released from pre adipose cells and behaves as a paracrine/autocrine effector of adipose cell differentiation, the present results favor a key role of prostacyclin by m eans of the IP receptor and its intracellular signaling pathway in elicitin g the critical early expression of both transcription factors. (C) 2000 Els evier Science Ireland Ltd. All rights reserved.