alpha-Trinositol (D-myo-inositol-1,2,6-trisphosphate), an isomer of the intracellular messenger IP3, has been studied for its anti-inflammatory and other effects in animal experiments and in human. The mechanisms of action remain unknown. Several human pathologies are associated with uncontrolled production of fibroblast growth factors (FGFs). FGF-2 induces vascular smooth muscle cell proliferation, which contributes to restenosis after coronary balloon angioplasty. The expression of several FGFs is also increased in tumors. We studied the effects of the water- and lipid-soluble derivatives of alpha-trinositol on the FGF-2-and/or FGF-8-induced proliferation of human pulmonary artery smooth muscle cells (HPASMC) and 5115 mouse breast cancer cells. a-Trinositol decreased the FGF-mediated proliferation of HPASMC and 5115 cells. Membrane permeability did not seem obligatory since the lipid-soluble form of alpha-trinositol was less effective than the water-soluble derivative. These results suggest a new biological function for certain phosphoinositides in the modulation of FGF-regulated processes. (C) 2004 Elsevier Inc. All rights reserved.