When hepatic stellate cells were stimulated by UTP, ATP, or ADP, cellular levels of inositol phosphates significantly increased (UTP > ATP > ADP > 5'-O-(3-thiotriphosphate). Thirty min after incubation with 100 microM of UTP, ATP, or ADP, levels of inositol monophosphate increased to 1318 +/- 116, 616 +/- 87 and 591 +/- 234% of control levels, respectively, with concomitant increase in the production of inositol trisphosphate and bisphosphate. These nucleotides transiently increased the [Ca2+]i of fura-2-loaded stellate cells. Moreover, UTP, ATP, ADP and adenosine 5'-O-(3-thiotriphosphate) were able to induce contraction of stellate cells as detected using the silicone-rubber membrane method. These results suggested that hepatic stellate cells have nucleotide receptors which react predominantly with extracellular UTP and ATP and trigger the receptor-mediated contraction of the cells.