We have previously reported that lysophosphatidic acid (LPA) sensitizes mechanical stress-induced cytosolic free Ca2+ concentration ([Ca2+]i) response related to Ca2+ entry through Gd(3+)-sensitive ion channels (Biochem. Biophys. Res. Commun. 208 19-25 1995). Here we examined the contribution of Ca2 release from intracellular stores to the mechanical stress-induced [Ca2+]i response sensitized by LPA in cultured longitudinal muscle cells from guinea pig ileum. Although the percentage of responsive cells to the mechanical stress in the presence of 30 nM LPA declined by decreasing extracellular Ca2+ concentration to less than 20 microM, the amplitude of the mechanical stress-induced [Ca2+]i transient did not depend on extracellular Ca2+ concentrations (10 microM-1.8 mM). The [Ca2+]i transient was completely abolished by treatment with thapsigargin. In addition, the amplitude of the [Ca2+]i transient gradually decreased after ryanodine and caffeine treatment. These results indicate that the mechanical stress-induced [Ca2+]i transient in the presence of LPA is mainly due to Ca2+ release from ryanodine-sensitive intracellular stores and may be triggered by Ca2+ influx through Gd(3+)-sensitive ion channels.