Journal article
Differential down-regulation of aquaporin-2 in rat kidney zones by peripheral nociceptin/orphanin FQ receptor agonism and vasopressin type-2 receptor antagonism
Department of Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark. niels.hadrup@gmail.com1
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-NH(2) (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 ( approximately 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.
Language: | English |
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Year: | 2007 |
Pages: | 516-24 |
ISSN: | 15210103 and 00223565 |
Types: | Journal article |
DOI: | 10.1124/jpet.107.123588 |