Abstract
We previously showed that aquaresis induced by the peripherally acting nociceptin/orphanin FQ receptor agonist ZP120 is associated with a decreased protein level of aquaporin-2 (AQP2) in whole-kidney homogenates. We now examined the effects of Ac-RYYRWKKKKKKK-NH2 (ZP120) (1 nmol/kg/min i.v. for 4 h) on renal regional expression (cortex/outer stripe of outer medulla, inner stripe of outer medulla, and inner medulla) and subcellular localization of aquaporin-2. Responses to ZP120 were compared to the effects of an equi-aquaretic dose (∼40% inhibition of distal water reabsorption) of the vasopressin type-2 receptor antagonist 5-dimethylamine-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzapine (OPC31260) (32 nmol/kg/min). ZP120 decreased the aquaporin-2 protein level in the rat cortex/outer stripe of outer medulla and decreased apical plasma membrane localization of aquaporin-2 in the cortex (P = 0.002) and in the inner medulla (P = 0.06). These effects were not accompanied by a decrease in the aquaporin-2 mRNA level. OPC31260-induced aquaresis was associated with a decreased aquaporin-2 protein level in both the cortex/outer stripe of outer medulla and in the inner stripe of outer medulla. Apical localization of aquaporin-2 was decreased throughout all kidney zones, and OPC31260 decreased the AQP2 mRNA level in the inner medulla. We conclude that equi-aquaretic doses of ZP120 and OPC31260 produce different patterns of aquaporin-2 down-regulation, suggesting different signaling pathways.
Footnotes
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This work was supported by The Danish Medical Research Council, The Danish Heart Foundation (03-1-2-13A-22051), The Eva and Robert Voss Hansen Foundation, The Ruth Kønig-Petersen Foundation, The Foundation of 17-12-1981, The Kong Christian den Tiendes Foundation, The Grosserer Valdemar Foersom and Spouse Thyra Foersom Foundation, The A. P. Møller Foundation for the Advancement of Medical Science, The Director E. Danielsen and Spouse Foundation, The Danish Kidney Association (Nyreforeningen), The Jacob Madsen and spouse Olga Madsen Foundation, Gigt-foreningen (Ingeniør af Frederikssund, Søren Alfred Andersens Legat), Director Kurt Bønnelycke and spouse Mrs. Grethe Bønnelyckes Foundation, The Mogens Svarre Mogensens Foundation, and The Beckett-Foundation.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.123588.
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ABBREVIATIONS: AVP, arginine-vasopressin; AQP2, aquaporin-2; CD, collecting duct; CLi, lithium clearance; Ctx, cortex; FELi, fractional lithium excretion; IM, inner medulla; ISOM, inner stripe of outer medulla; NOP, nociceptin/orphanin FQ receptor; OM, outer medulla; OPC31260, 5-dimethylamine-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzapine; OSOM, outer stripe of outer medulla; UNaV, urinary sodium excretion; GFR, glomerular filtration rate; ANOVA, analysis of variance; PCR, polymerase chain reaction; PBS, phosphate-buffered saline; V2, vasopressin-2; ZP120C, Ac-RYYRWKKKKKKK-NH2.
- Received April 18, 2007.
- Accepted August 1, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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