title: Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4.
abstract: Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE2receptor EP4Notably, EP4also controls urinary concentration through regulation of aquaporin 2 (AQP2). Here, we tested the hypothesis that sequential activation of EP4and PRR determines AQP2 expression in the CD, thus mediating the antidiuretic action of vasopressin (AVP). Water deprivation (WD) elevated renal PRR expression and urinary soluble PRR excretion in rats. Intrarenal infusion of a PRR decoy peptide, PRO20, or an EP4antagonist partially prevented the decrease in urine volume and the increase in urine osmolality and AQP2 expression induced by 48-hour WD. In primary cultures of rat inner medullary CD cells, AQP2 expression induced by AVP treatment for 24 hours depended on sequential activation of the EP4receptor and PRR. Additionally, mice lacking PRR in the CD exhibited increased urine volume and decreased urine osmolality under basal conditions and impaired urine concentrating capability accompanied by severe volume loss and a dangerous level of plasma hyperosmolality after WD. Together, these results suggest a previously undescribed linear AVP/PGE2/EP4/PRR pathway in the CD for regulation of AQP2 expression and urine concentrating capability.
authors.affiliation: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Kexin
authors.initials: K
authors.lastname: Peng
authors.affiliation: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Adam
authors.initials: A
authors.lastname: Nau
authors.affiliation: Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Yang
authors.affiliation: Department of Medicine II, Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan; and.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.affiliation: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
authors.affiliation: Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah; Tianxin.Yang@hsc.utah.edu.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000818:Animals; D004231:Diuresis / Q000502:physiology*; D007685:Kidney Tubules, Collecting; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000502:physiology*; D014667:Vasopressins / Q000502:physiology*; D000093342:Prorenin Receptor
chemical_list: D011956:Receptors, Cell Surface; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014667:Vasopressins; D000093342:Prorenin Receptor
keywords: (Pro)renin receptor; aquaporin-2; nephrogenic diabetes insipidus; prostaglandin EP4 receptor; vasopressin