Potential role of purinergic signaling in urinary concentration in inner medulla: insights from P2Y2 receptor gene knockout mice.
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.
Zhang
Yue
Y
Nephrology Research (151M VA SLC Health Care System, 500 Foothill Dr., Salt Lake City, UT 84148, USA.
Sands
Jeff M
JM
Kohan
Donald E
DE
Nelson
Raoul D
RD
Martin
Christopher F
CF
Carlson
Noel G
NG
Kamerath
Craig D
CD
Ge
Yuqiang
Y
Klein
Janet D
JD
Kishore
Bellamkonda K
BK
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
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