Lipoxygenase inhibitors suppress intracellular calcium rise induced by ionomycin in rat thymocytes

Abstract

The lipoxygenase (LO) inhibitors nordihydroguaiaretic acid (NDGA) and 16S-hydroxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-HETE) have been found to suppress the rise in free cytoplasmic Ca 2+ concentration ([Ca 2+] i) induced by the Ca 2+ ionophores ionomycin and A23187 in rat thymocytes. Bromophenacyl bromide (BPB), a phospholipase A 2 (PLA 2) inhibitor, produced a much weaker inhibitory effect, and indomethacin, a cyclo-oxygenase inhibitor, practically did not influence the [Ca 2+] i response to ionomycin. These findings implicate the involvement of LO product(s) in the [Ca 2+] i rise triggered by the Ca 2+ ionophores. The contribution of the NDGA-sensitive component to the ionomycin-induced [Ca 2+] i rise was significant in the ionomycin concentration range of 0.1 nM to 0.1 μM, whereas at higher doses of the ionophore it gradually diminished. By contrast, the [Ca 2+] i rise induced by exogenous arachidonic acid (AA) or melittin, a PLA 2 activator, was not suppressed but potentiated by NDGA. Ionomycin and exogenous AA also elicited opposite changes in thymocyte cytoplasmic pH (pH i): the former elevated the pH i while the latter induced a pronounced acidification of the cytoplasm. This difference in the pH i responses may account for the different sensitivity of ionomycin- and AA-elicited [Ca 2+] i signal to LO inhibitors.