Lipoxygenase inhibitors suppress intracellular calcium rise induced by ionomycin in rat thymocytes.
The lipoxygenase (LO) inhibitors nordihydroguaiaretic acid (NDGA) and 15S-hydroxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-HETE) have been found to suppress the rise in free cytoplasmic Ca2+ concentration [( Ca2+]i) induced by the Ca2+ ionophores ionomycin and A23187 in rat thymocytes. Bromophenacyl bromide (BPB), a phospholipase A2 (PLA2) inhibitor, produced a much weaker inhibitory effect, and indomethacin, a cyclo-oxygenase inhibitor, practically did not influence the [Ca2+]i response to ionomycin. These findings implicate the involvement of LO product(s) in the [Ca2+]i rise triggered by the Ca2+ ionophores. The contribution of the NDGA-sensitive component to the ionomycin-induced [Ca2+]i rise was significant in the ionomycin concentration range of 0.1 nM to 0.1 microM whereas at higher doses of the ionophore it gradually diminished. By contrast, the [Ca2+]i rise induced by exogenous arachidonic acid (AA) or melittin, a PLA2 activator, was not suppressed but potentiated by NDGA. Ionomycin and exogenous AA also elicited opposite changes in thymocyte cytoplasmic pH (pHi): the former elevated the pHi while the latter induced a pronounced acidification of the cytoplasm. This difference in the pHi responses may account for the different sensitivity of ionomycin- and AA-elicited [Ca2+]i signal to LO inhibitors.
Gukovskaya
A S
AS
Institute of Biological Physics, USSR Academy of Sciences, Pushchino, Moscow.
Arias Pulido
H
H
Petrunyaka
V V
VV
Zinchenko
V P
VP
Bezuglov
V V
VV
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D015759:Ionomycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology*; D008555:Melitten / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000098:Acetophenones; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D008555:Melitten; D016718:Arachidonic Acid; D000001:Calcimycin; D015759:Ionomycin; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D009637:Masoprocol; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide; D002118:Calcium; D007213:Indomethacin