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1 Department of Medicine, 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; Division of Pediatric Nephrology, University of Utah Health Sciences Center, Salt Lake City, UT, USA
2 Department of Biology, University of Dayton, Dayton, OH, USA
3 Nephrology Research, VA Salt Lake City Health Care System, Salt Lake City, UT, USA
4 Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA; Division of Pediatric Nephrology, University of Utah Health Sciences Center, Salt Lake City, UT, USA
* To whom correspondence should be addressed. E-mail: Bellamkonda.Kishore{at}hsc.utah.edu.
Arginine vasopressin (AVP), acting through cAMP second messenger system, regulates osmotic water permeability (Pf) of the collecting duct. In the collecting duct, the activities of cAMP and phosphonositides (PI) are mutually inhibitory. P2Y2 receptor (P2Y2-R) is a G protein-coupled extracellular nucleotide receptor associated with PI signaling pathway. Previously we showed that P2Y2-R is expressed in inner medullary collecting duct (IMCD) of rat, and its agonist (ATP/UTP) activation decreased AVP-induced Pf, and resulted in enhanced production of prostaglandin E2. Hydrated and dehydrated states are associated with alterations in the circulating levels of AVP, expression and/or subcellular distribution of AVP-regulated aqauaporin-2 water channel in IMCD and thus Pf of IMCD. We hypothesized that altered expression and/or signaling via P2Y2-R may also modulate IMCD function in these conditions. Sprague-Dawley rats were subjected to dehydration by water deprivation (48 h) or hydration (48 or 96 h) by providing sucrose water. Hydration or dehydration resulted in marked alterations in mRNA expression (Northern analysis and real-time RT-PCR) and protein abundance (Western analysis) of P2Y2-R, with hydrated rats showing significantly higher levels as compared to dehydrated rats. Sequential hydration and dehydration experiments also revealed that the regulated expression profiles of P2Y2-R mRNA and protein are discordant. Conversely, the expression of V2-R mRNA remained unaltered during hydration and dehydration. Since virtually all renal cells release ATP in a regulated fashion, the observed alterations in P2Y2-R expression in the inner medulla in hydrated and dehydrated states may constitute a novel mechanism of purinergic modulation of IMCD function.
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