title: Pendrin localizes to the adrenal medulla and modulates catecholamine release.
abstract: Pendrin (Slc26a4) is a Cl(-)/HCO3 (-) exchanger expressed in renal intercalated cells and mediates renal Cl(-) absorption. With pendrin gene ablation, blood pressure and vascular volume fall, which increases plasma renin concentration. However, serum aldosterone does not significantly increase in pendrin-null mice, suggesting that pendrin regulates adrenal zona glomerulosa aldosterone production. Therefore, we examined pendrin expression in the adrenal gland using PCR, immunoblots, and immunohistochemistry. Pendrin protein was detected in adrenal lysates from wild-type but not pendrin-null mice. However, immunohistochemistry and qPCR of microdissected adrenal zones showed that pendrin was expressed in the adrenal medulla, rather than in cortex. Within the adrenal medulla, pendrin localizes to both epinephrine- and norepinephrine-producing chromaffin cells. Therefore, we examined plasma catecholamine concentration and blood pressure in wild-type and pendrin-null mice under basal conditions and then after 5 and 20 min of immobilization stress. Under basal conditions, blood pressure was lower in the mutant than in the wild-type mice, although epinephrine and norepinephrine concentrations were similar. Catecholamine concentration and blood pressure increased markedly in both groups with stress. With 20 min of immobilization stress, epinephrine and norepinephrine concentrations increased more in pendrin-null than in wild-type mice, although stress produced a similar increase in blood pressure in both groups. We conclude that pendrin is expressed in the adrenal medulla, where it blunts stress-induced catecholamine release.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia;
authors.forename: Yoskaly
authors.initials: Y
authors.lastname: Lazo-Fernandez
authors.affiliation: Section on Endocrine Physiology, Developmental Endocrinology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland;
authors.forename: Greti
authors.initials: G
authors.lastname: Aguilera
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia;
authors.forename: Truyen D
authors.initials: TD
authors.lastname: Pham
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia;
authors.forename: Annie Y
authors.initials: AY
authors.lastname: Park
authors.affiliation: Hypertension and Vascular Research Division, Henry Ford Hospital and Wayne State School of Medicine, Detroit, Michigan;
authors.forename: William H
authors.initials: WH
authors.lastname: Beierwaltes
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Atlanta Veterans Affairs Hospital, Atlanta, Georgia;
authors.forename: Roy L
authors.initials: RL
authors.lastname: Sutliff
authors.affiliation: Department of Medicine, University of Florida, Gainesville, Florida;
authors.forename: Jill W
authors.initials: JW
authors.lastname: Verlander
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland;
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, Georgia;
authors.forename: Adeboye O
authors.initials: AO
authors.lastname: Osunkoya
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, Georgia;
authors.forename: Carla L
authors.initials: CL
authors.lastname: Ellis
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia;
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Houston, Texas;
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Shipley
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia;
authors.forename: Brandi M
authors.initials: BM
authors.lastname: Wynne
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Atlanta Veterans Affairs Hospital, Atlanta, Georgia; Department of Physiology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hoover
authors.affiliation: Cardiovascular Disease Section, and National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland;
authors.forename: Shurjo K
authors.initials: SK
authors.lastname: Sen
authors.affiliation: Department of Psychiatry, Emory University School of Medicine, Atlanta, Georgia; and.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Plotsky
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Department of Physiology, Emory University School of Medicine, Atlanta, Georgia smwall@emory.edu.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Wall
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics* / Q000378:metabolism; D001794:Blood Pressure; D027963:Chloride-Bicarbonate Antiporters / Q000235:genetics* / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism*; D020869:Gene Expression Profiling; D015151:Immunoblotting; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000378:metabolism*; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D027963:Chloride-Bicarbonate Antiporters; D012333:RNA, Messenger; C494615:Slc26A4 protein, rat; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters; D009638:Norepinephrine; D004837:Epinephrine
keywords: chloride; dopamine; epinephrine; norepinephrine; pendrin