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1 Department of Medicne, University of Utah Health Sciences Center, Salt Lake City, UT, USA; Department of Physiology, University of Utah Health Sciences Center, Salt Lake City, UT, USA; Nephrology Research, VA Salt Lake City Health Care System, Salt Lake City, UT, USA
2 Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City, UT, USA
3 Department of Medicne, University of Utah Health Sciences Center, Salt Lake City, UT, USA; Nephrology Research, VA Salt Lake City Health Care System, Salt Lake City, UT, USA
* To whom correspondence should be addressed. E-mail: Bellamkonda.Kishore{at}hsc.utah.edu.
Activation of P2Y2 receptor (P2Y2-R) in inner medullary collecting duct (IMCD) of rat
decreases AVP-induced water flow, and releases PGE2. We observed that dehydration of rats
decreases the expression of P2Y2-R in inner medulla (IM), and P2Y2-R-mediated PGE2 release by
IMCD. Since circulating vasopressin (AVP) levels are increased in dehydrated condition, we
examined whether chronic infusion of 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 PGE2 metabolite content were
determined. AQP2 and P2Y2 and V2 receptor mRNA and/or protein in IM were quantified by real-time
RT-PCR and immunoblotting, respectively. P2Y2-R-mediated PGE2 release by freshly
prepared IMCD was assayed using ATP
S 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
(~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 PGE2 release by IMCD
was significantly decreased in rats infused 20 ng/h, but not 5 ng/h of dDAVP. Urinary PGE2
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.
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