Differential down-regulation of aquaporin-2 in rat kidney zones by peripheral nociceptin/orphanin FQ receptor agonism and vasopressin type-2 receptor antagonism.
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.
Hadrup
Niels
N
Department of Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark. niels.hadrup@gmail.com
Petersen
Jørgen S
JS
Windfeld
Søren
S
Risom
Lotte
L
Andersen
Claus B
CB
Nielsen
Søren
S
Christensen
Sten
S
Jonassen
Thomas E N
TE
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D015536:Down-Regulation; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology*; D017483:Receptors, Vasopressin / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D000094942:Nociceptin Receptor
D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2; D001552:Benzazepines; D012333:RNA, Messenger; D011957:Receptors, Opioid; D017483:Receptors, Vasopressin; D012964:Sodium; D000094942:Nociceptin Receptor; C496025:Aqp2 protein, rat; C076251:mozavaptan; C000722285:Oprl1 protein, rat