Inositol(1,4,5)trisphosphate signal triggers a receptor-mediated ATP release

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 μM) elicited substantial release of ATP from the cells, but not from a human fibroblast cell line. However, Ang II even at 10 μM 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 μM SC52458, an AT 1 receptor antagonist, not by 10 μM PD123319, an AT 2 receptor antagonist. The evoked release of ATP was almost completely inhibited in the presence of 10 μM U73122, a phospholipase C inhibitor, and 0.5 μM thapsigargin, a Ca 2+-ATPase inhibitor. Furthermore, the release was hampered by 50 μM BAPTA/AM, an intracellular Ca 2+ chelator, but not by 0.1 μM nifedipine, a voltage gated Ca 2+ 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 Ca 2+ signals activated via stimulation of Ins(1,4,5)P 3 receptor are involved in the release of ATP evoked by Ang II.