Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Pharmacology and Experimental Therapeutics |
| Vol/bind | 323 |
| Udgave nummer | 2 |
| Sider (fra-til) | 516-24 |
| Antal sider | 8 |
| ISSN | 0022-3565 |
| DOI | |
| Status | Udgivet - 2007 |
Bibliografisk note
Keywords: Animals; Aquaporin 2; Benzazepines; Diuresis; Down-Regulation; Kidney; Male; RNA, Messenger; Rats; Rats, Wistar; Receptors, Opioid; Receptors, Vasopressin; SodiumAdgang til dokumentet
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I: Journal of Pharmacology and Experimental Therapeutics, Bind 323, Nr. 2, 2007, s. 516-24.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Differential down-regulation of aquaporin-2 in rat kidney zones by peripheral nociceptin/orphanin FQ receptor agonism and vasopressin type-2 receptor antagonism
AU - Hadrup, Niels
AU - Petersen, Jørgen S
AU - Windfeld, Søren
AU - Risom, Lotte
AU - Andersen, Claus B
AU - Nielsen, Søren
AU - Christensen, Sten
AU - Jonassen, Thomas
N1 - Keywords: Animals; Aquaporin 2; Benzazepines; Diuresis; Down-Regulation; Kidney; Male; RNA, Messenger; Rats; Rats, Wistar; Receptors, Opioid; Receptors, Vasopressin; Sodium
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1124/jpet.107.123588
DO - 10.1124/jpet.107.123588
M3 - Journal article
C2 - 17693587
SN - 0022-3565
VL - 323
SP - 516
EP - 524
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -