Opioid receptor-like 1 stimulation in the collecting duct induces aquaresis through vasopressin-independent aquaporin-2 downregulation.

Abstract

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 colocalized 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 analog ZP120C; volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 50 mM glucose. ZP120C induced a marked and sustained aquaresis in normal and congestive heart failure rats in the absence of changes in vasopressin plasma concentrations. The ZP120C-induced aquaresis was associated with downregulation 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 4 h 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 downregulation, through a mechanism not involving inhibition of vasopressin type-2 receptor-mediated cAMP production.

• Authors: Niels Hadrup, Jørgen S Petersen, Jeppe Praetorius, Eddi Meier, Martin Graebe, Lone Brønd, Dennis Staahltoft, Søren Nielsen, Sten Christensen, Daniel R Kapusta, Thomas E N Jonassen
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 287 Issue 1 Pg. F160-8 (Jul 2004) ISSN: 1931-857X [Print] United States
• PMID: 15010357 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aqp2 protein, rat
• Aquaporin 2
• Aquaporins
• Opioid Peptides
• Receptors, Opioid
• Vasodilator Agents
• Vasopressins
• Nociceptin Receptor
• Oprl protein, rat

Topics

• Animals
• Aquaporin 2
• Aquaporins (biosynthesis, metabolism)
• Down-Regulation
• Heart Failure (complications, physiopathology)
• Immunohistochemistry
• Infusions, Intravenous
• Kidney Tubules, Collecting (physiology)
• Male
• Opioid Peptides (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid (biosynthesis)
• Urine (chemistry)
• Vasodilator Agents (pharmacology)
• Vasopressins (pharmacology)
• Nociceptin Receptor
• Nociceptin