Prostaglandin E₂interaction with AVP: effects on AQP2 phosphorylation and distribution

Abstract

Prostaglandin E(2) (PGE(2)) antagonizes the action of arginine vasopressin (AVP) on collecting duct water permeability. To investigate the mechanism of this antagonism, rat renal inner medulla (IM) was incubated with the two hormones, and the phosphorylation and subcellular distribution of the water channel, aquaporin-2 (AQP2) were studied. Using a phosphorylation state-specific AQP2 antibody, we demonstrated that AVP stimulates AQP2 phosphorylation at the Ser(256) protein kinase A consensus site in a time- and dose-dependent manner. In parallel studies using a differential centrifugation technique, we demonstrated that AVP induced translocation of AQP2 from an intracellular vesicle-enriched fraction to a plasma membrane-enriched fraction. PGE(2) (10(-7) M) added after AVP (10(-8) M) did not decrease AQP2 phosphorylation but reversed AVP-induced translocation of AQP2 to the plasma membrane. Preincubation of IM with PGE(2) did not prevent the effects of AVP on AQP2 phosphorylation and trafficking. PGE(2) alone did not influence AQP2 phosphorylation and subcellular distribution. Our data indicate that 1) recruitment of AQP2 to the plasma membrane and its retrieval to a pool of intracellular vesicles may be regulated independently, 2) PGE(2) may counteract AVP action by activation of AQP2 retrieval, 3) dephosphorylation of AQP2 is not a prerequisite for its internalization.

The laxative effect of bisacodyl is attributable to decreased aquaporin-3 expression in the colon induced by increased PGE2secretion from macrophages

“…sacodyl activates macrophages in the colon (24,29). Furthermore, TNF-␣ (9,19,38) and PGE 2 (25,39) decrease the expression levels of AQPs. Based on this, we examined whether bisacodyl directly activated macrophages and caused the secretion of TNF-␣ and PGE 2 using Raw264.7 cells.…”

“…This result indicates the possibility that PGE 2 is involved in the drastic and immediate decrease in AQP3 in the mucosal epithelial cells in the colon induced by bisacodyl administration. Although the mechanism by which PGE 2 decreases AQP3 is not yet clear, it may increase the endocytosis and degradation of AQP3 (25,39).…”

Proteomic analysis of lithium-induced nephrogenic diabetes insipidus: Mechanisms for aquaporin 2 down-regulation and cellular proliferation

“…However, it has been shown that inhibition of GSK3␤ by lithium results in enhanced renal COX2 expression in interstitial cells, leading to an increase in local PGE(2) excretion (18), that in turn may counteract AVP actions by causing endocytic retrieval of AQP2 from the collecting duct plasma membrane, thus impairing urinary concentrating ability (20). GSK3␤ knockout mice die from liver degeneration (21); thus, the consequence of GSK3␤ gene deletion on kidney function has yet to be examined.…”

P2Y2 receptors and water transport in the kidney

“…We have demonstrated that P2Y 2 receptor-mediated PGE 2 release is markedly enhanced in physiological polyuria induced by water loading, and blunted in oliguria caused by water deprivation or chronic dDAVP (V 2 receptor-specific analogue of AVP) infusion in rats [31,32]. PGE 2 antagonises AVP-stimulated water permeability in the medullary collecting duct [7,9], an effect that is partly due to activation of EP (E-prostanoid)3 receptormediated retrieval of AQP2 from the apical membrane [13]. In addition, PGE 2 can chronically elevate phoshoinositides and thus potentially reduce the cAMP levels (Fig.…”

“…Apart from AVP, a variety of autocrine and paracrine agents, such as prostaglandin E 2 (PGE 2 ), endothelin and extracellular nucleotides (ATP/UTP), can regulate collecting duct water transport [7][8][9][10][11][12][13][14]. Acting through their respective receptors, and the associated phosphoinositide signalling pathway, these agents decrease AVP-stimulated osmotic water permeability in the collecting duct (Fig.…”