Noncyclooxygenase metabolites of arachidonic acid amplify the vasopressin-induced Ca2+ signal in glomerular mesangial cells by releasing Ca2+ from intracellular stores.

摘要: Noncyclooxygenase metabolites of arachidonic acid may be potent modulators the mitogenic response renal mesangial cells to vasoactive peptide arginine vasopressin (AVP). Since Ca2+ is a critical second messenger in AVP, and has been implicated regulation growth, we determined whether noncyclooxygenase altered phospholipase C-Ca2+ signalling cascade which activated by AVP. Pretreatment for 10 min with lipoxygenase cytochrome P450 monooxygenase inhibitors, nordihydroguaiaretic (NDGA, 10(-5) M) or SKF-525A (2.5 x M), but not cyclooxygenase inhibitor indomethacin (2 reduced magnitude AVP (10(-8) 10(-7) M)-induced increase cytosolic free concentration ([Ca2+]i) without affecting inositol trisphosphate production. With 10(-8) M [Ca2+]i increased 250 +/- 47 nM NDGA-treated versus 401 59 control (p less than 0.01). [Ca2+]i, measured 2 after exposure was also lower NDGA (152 21 nM) when compared alone (220 22 nM, p 14,15-epoxyeicosatrienoic (EET) had no effect on production, completely reversed NDGA-induced inhibition transient, whereas 5-hydroperoxyeicosatetraenoic (HPETE) (5 did not. higher concentrations 14,15-EET (10(-7)-10(-6) markedly potentiated AVP-induced [Ca2+]i. AVP-generated transient observed were incubated low media ([Ca2+] 5 suggesting that pretreatment impaired intracellular release Ca2+. direct 1,4,5-trisphosphate-induced release, postulated blocked production metabolite releases from stores. 15-HPETE, 15-hydroxyeicosatetraenoic (each at 3 raised added directly media. In permeabilized 15-HPETE (10(-7) potently released summary, acid, particular metabolites, are endogenous amplifiers signal mechanisms involving C activation. This mediated, least part, enhanced storage sites an 1,4,5-trisphosphate-independent mechanism.