title: Cortisol regulates Na+ uptake in zebrafish, Danio rerio, larvae via the glucocorticoid receptor.
abstract: Unlike other freshwater fish previously examined, zebrafish are capable of increasing their rate of Na(+) uptake during chronic exposure to acidic water (pH 4). In the present study, the potential role of cortisol in the induction of Na(+) uptake during acid-exposure was investigated. When zebrafish larvae (4 days post-fertilization) were treated with waterborne cortisol, the rate of Na(+) uptake was significantly increased; this effect was blocked by co-incubating larvae with RU-486, an antagonist selective for the glucocorticoid receptor (GR). A similar induction in Na(+) uptake, which was also blocked by RU-486, was observed when larvae were treated with dexamethasone, a selective GR agonist. Conversely, treating larvae with aldosterone, a selective agonist for the mineralocorticoid receptor (MR) had no effect on Na(+) uptake. Acid-exposure increased whole body cortisol levels and translational knockdown of GR using antisense morpholinos prevented the full induction of Na(+) uptake during exposure to acidic water, further confirming the role of cortisol and GR in Na(+) uptake stimulation. Using immunohistochemistry, GR was localized to ionocytes known to be responsible for Na(+) uptake (HR-cells). Knockdown of Rhcg1, an apical membrane ammonia channel or Na(+)/H(+) exchanger 3b (NHE3b), proteins known to play an important role in facilitating Na(+) uptake in acidic water, prevented the stimulatory effects of cortisol treatment on Na(+) uptake, suggesting that cortisol regulates Na(+) uptake by stimulating an Rhcg1-NHE3b "functional metabolon".
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kumai
authors.forename: Dinushan
authors.initials: D
authors.lastname: Nesan
authors.forename: Mathilakath M
authors.initials: MM
authors.lastname: Vijayan
authors.forename: Steve F
authors.initials: SF
authors.lastname: Perry
mesh_terms: D000064:Acclimatization; D000450:Aldosterone / Q000494:pharmacology; D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects; D007814:Larva / Q000187:drug effects / Q000502:physiology; D015735:Mifepristone / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000819:agonists / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D027682:Cation Transport Proteins; D006727:Hormone Antagonists; D034741:RNA, Small Interfering; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D029961:Zebrafish Proteins; C524419:rhcgb protein, zebrafish; D015735:Mifepristone; D000450:Aldosterone; D000641:Ammonia; D003907:Dexamethasone; D012964:Sodium; D006854:Hydrocortisone