title: Chronic dDAVP infusion in rats decreases the expression of P2Y2 receptor in inner medulla and P2Y2 receptor-mediated PGE2 release by IMCD.
abstract: Activation of P2Y2 receptor (P2Y2-R) in inner medullary collecting duct (IMCD) of rat decreases AVP-induced water flow and releases PGE(2). We observed that dehydration of rats decreases the expression of P2Y2 receptor in inner medulla (IM) and P2Y2-R-mediated PGE(2) release by IMCD. Because circulating vasopressin (AVP) levels are increased in dehydrated condition, we examined whether chronic infusion of desmopressin (dDAVP) has a similar effect on the expression and activity of P2Y2-R. Groups of rats were infused with saline or dDAVP (5 or 20 ng/h sc, 5 or 6 days) via osmotic minipumps and euthanized. Urine volume, osmolality, and PGE(2) metabolite content were determined. AQP2- and P2Y2- and V2-R mRNA and/or protein in IM were quantified by real-time RT-PCR and immunoblotting, respectively. P2Y2-R-mediated PGE(2) release by freshly prepared IMCD was assayed using ATPgammaS as a ligand. Chronic dDAVP infusion resulted in low-output of concentrated urine and significantly increased the AQP2 protein abundance in IM. On the contrary, dDAVP infusion at 5 or 20 ng/h significantly decreased P2Y2-R protein abundance (approximately 40% of saline-treated group). In parallel, the relative expression of P2Y2-R vs. AQP2- or V2-R mRNA was significantly decreased. Furthermore, the P2Y2-R-mediated PGE(2) release by IMCD was significantly decreased in rats infused 20 ng/h but not 5 ng/h of dDAVP. Urinary PGE(2) metabolite excretion, however, did not change with dDAVP infusion. In conclusion, chronic dDAVP infusion decreases the expression and activity of P2Y2-R in IM. This may be due to a direct effect of dDAVP or dDAVP-induced increase in medullary tonicity.
authors.affiliation: Nephrology Research (151M VA Salt Lake City Health Care System, 500 Foothill Dr., Salt Lake City, UT 84148, USA.
authors.forename: Rujia
authors.initials: R
authors.lastname: Sun
authors.forename: R Lance
authors.initials: RL
authors.lastname: Miller
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hemmert
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Huihui
authors.initials: H
authors.lastname: Shi
authors.forename: Raoul D
authors.initials: RD
authors.lastname: Nelson
authors.forename: Bellamkonda K
authors.initials: BK
authors.lastname: Kishore
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D051399:Aquaporin 2; D020346:Aquaporins / Q000378:metabolism; D015153:Blotting, Western; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D007262:Infusions, Intravenous; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis* / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2; D012076:Renal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014563:Urodynamics / Q000187:drug effects
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D020346:Aquaporins; D017931:DNA Primers; D018076:DNA, Complementary; C546387:P2ry2 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D012076:Renal Agents; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D003894:Deamino Arginine Vasopressin; D015232:Dinoprostone