Potential role of 12 hydroxyeicosatetraenoic acid in angiotensin ii-induced calcium signal in rat glomerulosa cells

Naftali Stern, Norimoto Yanagawa, Fumio Saito, Mark Hori, Rama Natarajan, Jerry Nadler, Michael Tuck

Research output: Contribution to journalArticlepeer-review


Recent evidence suggests that 12 hydroxyeicosatetraenoic acid (12HETE), a product of the 12 lipoxygenase (LO) pathway of arachidonic acid metabolism, may have a role in mediating angiotensin II (All)-induced aldosterone secretion. The present study examined the possible role of the 12 LO product 12HETE in All-induced calcium ([Ca++]i) signals in rat glomerulosa cells. The addition of 12HETE to glomerulosa cells induced a dose-dependent (10-6-10-8 M) rise in [Ca++]i levels that was sustained over 15 min. The effects of 12HETE on [Ca++]i were attenuated but not blocked by nifedipine (5. 10-6 M) and were preserved in a calcium-free medium, suggesting mobilization of intracellular calcium stores. Furthermore, the 12HETE-mediated rise in [Ca++]i was almost entirely abolished by dantrolene. In parallel, 12HETE reversed the inhibitory effect of nifedipine on All-induced aldosterone secretion [All (10-9 M) -36 ± 7, All + nifedipine (5. 10-6M) - 13 ± 2, All + nifedipine + 12HETE (5. 10-8 M) - 27 ± 4 ng/106cells]. Dantrolene also inhibited All-dependent aldosterone secretion (All 10-9 M - 75.8 ± 5.6, All + dantrolene 10-6 M 45.5 ± 8.8 ng/10-6cells), but this inhibition could not be reversed by 12HETE 10-8 m (45.4 ± 10.6 ng/106 cells). The LO blockers baicalein and BW755C inhibited the effect of All on aldosterone production and on [Ca++]; in a parallel fashion. During LO blockade, the addition of 12HETE (10-7M) restored the All-induced rise in [Ca++]i- Collectively, these observations suggest that activation of the LO pathway in the rat adrenal glomerulosa contributes to changes in cytosolic calcium, which may be important for the steroidogenic effect of AIL.

Original languageEnglish
Pages (from-to)843-847
Number of pages5
Issue number2
StatePublished - Aug 1993


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