title: Secretin is involved in sodium conservation through the renin-angiotensin-aldosterone system.
abstract: Secretin (SCT) and its receptor (SCTR) are important in fluid regulation at multiple levelsviathe modulation of expression and translocation of renal aquaporin 2 and functions of central angiotensin II (ANGII). The functional interaction of SCT with peripheral ANGII, however, remains unknown. As the ANGII-aldosterone axis dominates the regulation of renal epithelial sodium channel (ENaC) function, we therefore tested whether SCT/SCTR can regulate sodium homeostasisviathe renin-angiotensin-aldosterone system. SCTR-knockout (SCTR-/-) mice showed impaired aldosterone synthase (CYP11B2) expression and, consequently, aldosterone release upon intraperitoneal injection of ANGII. Endogenous ANGII production induced by dietary sodium restriction was higher in SCTR-/-than in C57BL/6N [wild-type (WT)] mice, but CYP11B2 and aldosterone synthesis were not elevated. Reduced accumulation of cholesteryl ester-the precursor of aldosterone-was observed in adrenal glands of SCTR-/-mice that were fed a low-sodium diet. Absence of SCTR resulted in elevated basal transcript levels of adrenal CYP11B2 and renal ENaCs. Although transcript and protein levels of ENaCs were similar in WT and SCTR-/-mice under sodium restriction, ENaCs in SCTR-/-mice were less sensitive to amiloride hydrochloride. In summary, the SCT/SCTR axis is involved in aldosterone precursor uptake, and the knockout of SCTR results in defective aldosterone biosynthesis/release and altered sensitivity of ENaCs to amiloride.-Bai, J., Chow, B. K. C. Secretin is involved in sodium conservation through the renin-angiotensin-aldosterone system.
authors.affiliation: School of Biological Sciences, University of Hong Kong, Hong Kong, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Bai
authors.affiliation: School of Biological Sciences, University of Hong Kong, Hong Kong, China bkcc@hku.hk.
authors.forename: Billy K C
authors.initials: BK
authors.lastname: Chow
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System; D012633:Secretin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D012982:Sodium, Dietary / Q000378:metabolism*
chemical_list: D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; D012982:Sodium, Dietary; C029937:secretin receptor; D000804:Angiotensin II; D012633:Secretin; D000450:Aldosterone; D000584:Amiloride; D012964:Sodium; D019405:Cytochrome P-450 CYP11B2
keywords: CYP11B2; SCTR; epithelial sodium channels