title: Cyclooxygenase-2 mediates induction of the renal stanniocalcin-1 gene by arginine vasopressin.
abstract: In rats and mice, the renal stanniocalcin-1 (STC-1) gene is expressed in most nephron segments, but is differentially induced in response to dehydration. In cortical segments STC-1 mRNA levels are upregulated by the hypertonicity of dehydration, while hypovolemia causes gene induction in the inner medulla (papilla). In both cases induction is mediated by arginine vasopressin (AVP) acting via the V2 receptor (V2R). The intent of STC-1 gene upregulation during dehydration has yet to be established. Therefore, to narrow down the range of possible actions, we mapped out the pathway by which V2R occupancy upregulates the gene. V2R occupancy activates two different renal pathways in response to dehydration. The first is antidiuretic in nature and is mediated by direct V2R occupancy. The second pathway is indirect and counter-regulates AVP-mediated antidiuresis. It involves COX-2 (cyclooxygenase-2) and the prostanoids, and is activated by the V2R-mediated rise in medullary interstitial osmolality. The resulting prostanoids counter-regulate AVP-mediated antidiuresis. They also upregulate renal cytoprotective mechanisms. The present studies employed models of COX inhibition and COX gene deletion to address the possible involvement of the COX pathway. The results showed that both general and specific inhibitors of COX-2 blocked STC-1 gene induction in response to dehydration. Gene induction in response to dehydration was also abolished in COX-2 null mice (cortex and papilla), but not in COX-1 null mice. STC-1 gene induction in response to V2R occupancy was also uniquely abolished in COX-2 nulls (both regions). These findings therefore collectively suggest that AVP-mediated elevations in STC-1 gene expression are wholly dependent on functional COX-2 activity. As such, a permissive role for STC-1 in AVP-mediated antidiuresis can be ruled out, and its range of possible actions has been narrowed down to AVP counter-regulation and renal cytoprotection.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada; Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Law
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hébert
authors.forename: Rania
authors.initials: R
authors.lastname: Nasrallah
authors.forename: Robert
authors.initials: R
authors.lastname: Langenbach
authors.forename: Chris K C
authors.initials: CK
authors.lastname: Wong
authors.forename: Graham F
authors.initials: GF
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D003681:Dehydration / Q000201:enzymology / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology; D007679:Kidney Medulla / Q000201:enzymology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009399:Nephrons / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000819:agonists / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D006023:Glycoproteins; D018045:Receptors, Oxytocin; D001127:Arginine Vasopressin; C051795:teleocalcin; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: COX-2; Kidney; Prostanoids; Stanniocalcin-1; Vasopressin