title: Potential role of 12 hydroxyeicosatetraenoic acid in angiotensin II-induced calcium signal in rat glomerulosa cells.
abstract: 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 (AII)-induced aldosterone secretion. The present study examined the possible role of the 12 LO product 12HETE in AII-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 x 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 AII-induced aldosterone secretion [AII (10(-9) M) - 36 +/- 7, AII + nifedipine (5 x 10(-6) M) - 13 +/- 2, AII + nifedipine + 12HETE (5 x 10(-8) M) - 27 +/- 4 ng/10(6) cells]. Dantrolene also inhibited AII-dependent aldosterone secretion (AII 10(-9) M - 75.8 +/- 5.6, AII + dantrolene 10(-6) M 45.5 +/- 8.8 ng/10(-6) cells), but this inhibition could not be reversed by 12HETE 10(-8) M (45.4 +/- 10.6 ng/10(6) cells). The LO blockers baicalein and BW755C inhibited the effect of AII on aldosterone production and on [Ca++]i in a parallel fashion. During LO blockade, the addition of 12HETE (10(-7) M) restored the AII-induced rise in [Ca++]i. Collectively, these observations suggest that activation of the LO pathway in the rat adrenal glomerulosa contributes to change in cytosolic calcium, which may be important for the steroidogenic effect of AII.
authors.affiliation: Section of Endocrinology, Sourasky-Tel-Aviv Medical Center, Ichilov Hospital, Tel-Aviv, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Stern
authors.forename: N
authors.initials: N
authors.lastname: Yanagawa
authors.forename: F
authors.initials: F
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: R
authors.initials: R
authors.lastname: Natarajan
authors.forename: J
authors.initials: J
authors.lastname: Nadler
authors.forename: M
authors.initials: M
authors.lastname: Tuck
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003620:Dantrolene / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D000804:Angiotensin II; D000450:Aldosterone; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase; D003620:Dantrolene; D009543:Nifedipine; D002118:Calcium