期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 288, 期 6, 页码 F1164-F1172出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00199.2004
关键词
purinergic; V2; cAMP; prostanoids; nucleotides
资金
- NIDDK NIH HHS [DK-53990, DK-61183] Funding Source: Medline
Arginine vasopressin (AVP), acting through a cAMP second messenger system, regulates osmotic water permeability (P(f)) of the collecting duct. In the collecting duct, the activities of cAMP and phosphonositides (PI) are mutually inhibitory. The 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 P(f) and resulted in enhanced production of prostaglandin E(2). Hydrated and dehydrated states are associated with alterations in the circulating levels of AVP, expression and/or subcellular distribution of AVP-regulated aquaporin-2 water channel in IMCD and thus P(f) 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 blot analysis and real-time RT-PCR) and protein abundance (Western blot analysis) of P2Y2-R, with hydrated rats showing significantly higher levels compared with 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. Because 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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