Intracellular signal transduction pathways involved in ATP release evoked by angiotensin II (Ang II) were investigated in cultured guinea pig Taenia coli smooth muscle cells. Ang II (0.3-1 muM) elicited substantial release of ATP from the cells, but not from a human fibroblast cell line. However, Ang II even at 10 muM failed to cause a leakage of lactate dehydrogenase (LDH) from the smooth muscle cells. The release of ATP by Ang II was suppressed by 10 muM SC52458, an AT(1) receptor antagonist, not by 10 muM PD123319, an AT(2) receptor antagonist. The evoked release of ATP was almost completely inhibited in the presence of 10 muM U73122. a phospholipase C inhibitor, and 0.5 muM thapsigargin, a Ca2+-ATPase inhibitor. Furthermore, the release was hampered by 50 muM BAPTA/AM, an intracellular Ca2+ chelator, but not by 0.1 muM nifedipine, a voltage gated Ca2+ channel inhibitor. The basal release of ATP was increased by BAPTA/AM, but was reduced by U-73122. Ang II enhanced instantaneously inositol(1,4,5)trisphosphate (Ins(1,4,5)P-3) accumulation in the cells. The enhancing effect was perfectly antagonized by SC52458. These findings suggest that intracellular Ca2+ signals activated via stimulation of Ins(1,4,5)P-3 receptor are involved in the release of ATP evoked by Ang II. (C) 2002 Elsevier Science (USA). All rights reserved.