title: Potential role of purinergic signaling in urinary concentration in inner medulla: insights from P2Y2 receptor gene knockout mice.
abstract: Osmotic reabsorption of water through aquaporin-2 (AQP2) in the inner medulla is largely dependent on the urea concentration gradients generated by urea transporter (UT) isoforms. Vasopressin (AVP) increases expression of both AQP2 and UT-A isoforms. Activation of the P2Y2 receptor (P2Y2-R) in the medullary collecting duct inhibits AVP-induced water flow. To gain further insights into the overarching effect of purinergic signaling on urinary concentration, we compared the protein abundances of AQP2 and UT-A isoforms between P2Y2-R knockout (KO) and wild-type (WT) mice under basal conditions and following AVP administration. Under basal conditions (a gel diet for 10 days), KO mice concentrated urine to a significantly higher degree, with 1.8-, 1.66-, and 1.29-fold higher protein abundances of AQP2, UT-A1, and UT-A2, respectively, compared with WT, despite comparable circulating AVP levels in both groups. Infusion of 1-desamino-8-d-arginine vasopressin (dDAVP; desmopressin; 1 ng/h sc) for 5 days resulted in 2.14-, 2.6-, and 2.22-fold higher protein abundances of AQP2, AQP3, and UT-A1, respectively, in the inner medullas of KO mice compared with WT mice. In response to acute (45 min) stimulation by AVP (0.2 unit/mouse sc), UT-A1 protein increased by 1.39- and 1.54-fold in WT and KO mice, respectively. These data suggest that genetic deletion of P2Y2-R results in increased abundances of key proteins involved in urinary concentration in the inner medulla, both under basal conditions and following AVP administration. Thus purinergic regulation may play a potential overarching role in balancing the effect of AVP on the urinary concentration mechanism.
authors.affiliation: Nephrology Research (151M VA SLC Health Care System, 500 Foothill Dr., Salt Lake City, UT 84148, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Sands
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
authors.forename: Raoul D
authors.initials: RD
authors.lastname: Nelson
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Martin
authors.forename: Noel G
authors.initials: NG
authors.lastname: Carlson
authors.forename: Craig D
authors.initials: CD
authors.lastname: Kamerath
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Ge
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
authors.forename: Bellamkonda K
authors.initials: BK
authors.lastname: Kishore
mesh_terms: D000042:Absorption; D000818:Animals; D051399:Aquaporin 2 / Q000502:physiology; D051400:Aquaporin 3 / Q000502:physiology; D051401:Aquaporin 4 / Q000502:physiology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D007679:Kidney Medulla / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018048:Receptors, Purinergic P2 / Q000172:deficiency* / Q000502:physiology; D058473:Receptors, Purinergic P2Y2; D014667:Vasopressins / Q000494:pharmacology
chemical_list: C496024:Aqp2 protein, mouse; C496028:Aqp3 protein, mouse; C496031:Aqp4 protein, mouse; D051399:Aquaporin 2; D051401:Aquaporin 4; C546386:P2ry2 protein, mouse; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D014667:Vasopressins; D051400:Aquaporin 3; D003894:Deamino Arginine Vasopressin