title: Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal Na+ and water excretion or arterial pressure.
abstract: cAMP is a key mediator of connecting tubule and collecting duct (CD) Na(+) and water reabsorption. Studies performed in vitro have suggested that CD adenylyl cyclase (AC)3 partly mediates the actions of vasopressin; however, the physiological role of CD AC3 has not been determined. To assess this, mice were developed with CD-specific disruption of AC3 [CD AC3 knockout (KO)]. Inner medullary CDs from these mice exhibited 100% target gene recombination and had reduced ANG II- but not vasopressin-induced cAMP accumulation. However, there were no differences in urine volume, urinary urea excretion, or urine osmolality between KO and control mice during normal water intake or varying degrees of water restriction in the presence or absence of chronic vasopressin administration. There were no differences between CD AC3 KO and control mice in arterial pressure or urinary Na(+) or K(+) excretion during a normal or high-salt diet, whereas plasma renin and vasopressin concentrations were similar between the two genotypes. Patch-clamp analysis of split-open cortical CDs revealed no difference in epithelial Na(+) channel activity in the presence or absence of vasopressin. Compensatory changes in AC6 were not responsible for the lack of a renal phenotype in CD AC3 KO mice since combined CD AC3/AC6 KO mice had similar arterial pressure and renal Na(+) and water handling compared with CD AC6 KO mice. In summary, these data do not support a significant role for CD AC3 in the regulation of renal Na(+) and water excretion in general or vasopressin regulation of CD function in particular.
authors.affiliation: Div. of Nephrology, Univ. of Utah Health Sciences Center, 1900 East 30 North, Salt Lake City, UT 84132. donald.kohan@hsc.utah.edu.
authors.forename: Wararat
authors.initials: W
authors.lastname: Kittikulsuth
authors.forename: Deborah
authors.initials: D
authors.lastname: Stuart
authors.forename: Alfred N
authors.initials: AN
authors.lastname: Van Hoek
authors.forename: James D
authors.initials: JD
authors.lastname: Stockand
authors.forename: Vladislav
authors.initials: V
authors.lastname: Bugaj
authors.forename: Elena
authors.initials: E
authors.lastname: Mironova
authors.forename: Mitsi A
authors.initials: MA
authors.lastname: Blount
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
mesh_terms: D000262:Adenylyl Cyclases / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis; D005260:Female; D007685:Kidney Tubules, Collecting / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012964:Sodium / Q000652:urine*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
chemical_list: D017673:Sodium Chloride, Dietary; D012964:Sodium; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6
keywords: adenylyl cyclase 3; blood pressure; collecting duct; gene targeting; urinary sodium and water excretion