| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pharmacology, University of Copenhagen, Copenhagen, Denmark
2 Zealand Pharma A/S, Glostrup, Denmark
3 The Water and Salt Research Center, Department of Anatomy, University of Aarhus, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: niels.hadrup{at}farmakol.ku.dk.
Nociceptin, the endogenous ligand of the inhibitory G-protein coupled opioid receptor-like 1 receptor produces aquaresis (i.e increases the excretion of solute free urine) in rats. However, the mechanism underlying this effect has not yet been explained. Using immunohistochemistry we found the opioid receptor-like 1 receptor in the rat kidney, co-localized with the vasopressin regulated water channel aquaporin-2 in inner medullary collecting ducts. We investigated the aquaretic effect of opioid receptor-like 1 receptor stimulation by infusing the selective nociceptin analogue ZP120C; volume depletion was prevented by computer-driven, servo-controlled i.v. volume replacement with 50 mM glucose. ZP120C induced a marked and sustained aquaresis, in normal and congestive heart failure rats, in absence of changes in vasopressin plasma concentrations. The ZP120C induced aquaresis was associated with down-regulation of the aquaporin-2 protein level in both rat groups suggesting that opioid receptor-like 1 receptor stimulation produces aquaresis by inhibiting the vasopressin type-2 receptor mediated stimulation on collecting duct water reabsorption. However, substantial amounts of PKA-mediated serine-256 phosphorylated aquaporin-2 were still present after four hours of ZP120C treatment. Furthermore, neither preincubation with nociceptin nor ZP120C inhibited vasopressin-mediated cAMP accumulation in isolated collecting ducts. We conclude that renal opioid receptor-like 1 receptor stimulation, in normal and congestive heart failure rats, produces aquaresis by a direct renal effect, via aquaporin-2 down regulation, through a mechanism not involving inhibition of vasopressin type-2 receptor mediated cAMP production.
This article has been cited by other articles:
|
|
 |
|
  U. S. K. van Deurs, N. Hadrup, J. S. Petersen, S. Christensen, and T. E. N. Jonassen Nociceptin/Orphanin FQ Peptide Receptor Agonist Ac-RYYRWKKKKKKK-NH2 (ZP120) Induces Antinatriuresis in Rats by Stimulation of Amiloride-Sensitive Sodium Reabsorption J. Pharmacol. Exp. Ther., February 1, 2009; 328(2): 533 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hadrup, J. S. Petersen, S. Windfeld, L. Risom, C. B. Andersen, S. Nielsen, S. Christensen, and T. E. N. Jonassen Differential Down-Regulation of Aquaporin-2 in Rat Kidney Zones by Peripheral Nociceptin/Orphanin FQ Receptor Agonism and Vasopressin Type-2 Receptor Antagonism J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 516 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Brond, N. Hadrup, N. Salling, M. Torp, M. Graebe, S. Christensen, S. Nielsen, and T. E. N. Jonassen Uncoupling of vasopressin signaling in collecting ducts from rats with CBL-induced liver cirrhosis Am J Physiol Renal Physiol, October 1, 2004; 287(4): F806 - F815. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
