P2Y2 receptor-mediated release of prostaglandin E2 by IMCD is altered in hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function.

نویسندگان

  • Rujia Sun
  • Noel G Carlson
  • Andrew C Hemmert
  • Bellamkonda K Kishore
چکیده

Circulating vasopressin levels change in hydrated and dehydrated conditions and thus control osmotic water permeability (P(f)) of the inner medullary collecting duct (IMCD). Prostaglandin E2 (PGE2) antagonizes vasopressin-induced P(f) of IMCD. Previously, we showed that activation of P2Y2 receptor (P2Y2-R) in IMCD results in production and release of PGE2, and P2Y2-R mRNA and protein are significantly elevated in inner medullas of hydrated rats compared with dehydrated rats. Therefore, we examined whether the altered expression of P2Y2-R in hydrated and dehydrated states is associated with corresponding changes in P2Y2-R-mediated PGE2 release by the IMCD. Rats were hydrated by providing sucrose water as the sole drinking fluid or dehydrated by water deprivation for 2 days. This resulted in high output-low osmolality and low output-high osmolality urines in hydrated and dehydrated rats, respectively. In hydrated rats, there was a significant increase in tubular fluid PGE2, measured indirectly by assessing the urinary PGE2 metabolite. Stimulation of freshly isolated IMCD preparations in vitro with P2Y2-R agonist (ATPgammaS) showed a marked increase in the release of PGE2 in hydrated rats compared with normal rats. These responses were blunted in the IMCD prepared from dehydrated rats. The P2Y2-R-mediated PGE2 release in the IMCD of hydrated rats was mediated largely by cyclooxygenase (COX)-1 as COX-1-specific inhibitor valeroyl salicylate completely blocked the release. The COX-2-specific inhibitor N5398 had only a modest and insignificant inhibitory effect. In conclusion, the increased sensitivity of purinergic-prostanoid interaction seen in the IMCD of hydrated rats may represent a novel vasopressin-independent regulatory mechanism of IMCD function.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

P2Y2 receptor mRNA and protein expression is altered in inner medullas of hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function.

Arginine vasopressin (AVP), acting through a 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. 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...

متن کامل

Chronic dDAVP infusion in rats decreases the expression of P2Y2 receptor in inner medulla and P2Y2 receptor-mediated PGE2 release by IMCD.

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 ...

متن کامل

Molecular and biochemical characterization of prostacyclin receptors in rat kidney.

The prostacyclin (IP) message was detected by RT-PCR in the renal cortex, outer (OM) and inner medulla (IM), and in freshly isolated (IMCD-f) and cultured inner medullary collecting duct (IMCD-c), and also the E-prostanoid (EP)1,3,4 receptor subtypes, but not EP2. Digoxigenin in situ hybridization localized IP mRNA in the tubules of the OM and IM, and the vasculature, and also in the glomeruli,...

متن کامل

Vasopressin-elicited water and urea permeabilities are altered in IMCD in hypercalcemic rats.

To investigate how hypercalcemia blunts renal concentrating ability, alterations in basal and arginine vasopressin (AVP)-elicited osmotic water ( P f) and urea ( P urea) permeabilities were measured in isolated perfused terminal inner medullary collecting ducts (IMCD) from control and chronically hypercalcemic rats after dihydrotachysterol (DHT) (M. Levi, L. Peterson, and T. Berl. Kidney Int. 2...

متن کامل

Downregulation of the V2 vasopressin receptor in dehydration: mechanisms and role of renal prostaglandin synthesis.

The vasopressin-aquaporin 2 system plays a key role in urine concentration in dehydration. In contrast to the upregulation of aquaporin 2, the downregulation of the vasopressin V2 receptor in dehydration is known. We investigated the mechanisms of this downregulation in dehydration using reverse transcription-competitive polymerase chain reaction (RT-competitive PCR) and Western blot analysis. ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • American journal of physiology. Renal physiology

دوره 289 3  شماره 

صفحات  -

تاریخ انتشار 2005