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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Nociceptin/Orphanin FQ Peptide Receptor Agonist Ac-RYYRWKKKKKKK-NH2 (ZP120) Induces Antinatriuresis in Rats by Stimulation of Amiloride-Sensitive Sodium Reabsorption

Ulla S. K. van Deurs, Niels Hadrup, Jørgen Søberg Petersen, Sten Christensen and Thomas E. N. Jonassen
Journal of Pharmacology and Experimental Therapeutics February 2009, 328 (2) 533-539; DOI: https://doi.org/10.1124/jpet.108.144774
Ulla S. K. van Deurs
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Niels Hadrup
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Jørgen Søberg Petersen
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Sten Christensen
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Thomas E. N. Jonassen
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Abstract

The aim of the present study was to examine the mechanisms responsible for the antinatriuretic effect of the selective, peripherally acting, nociceptin/orphanin FQ peptide (NOP) receptor partial agonist Ac-RYYRWKKKKKKK-NH2 (ZP120). Using immunohistochemistry, we showed that in the cortex NOP receptors are expressed in the distal convoluted tubules, the connecting tubules, and the collecting ducts. Using clearance techniques, we evaluated renal excretory function during acute administration of ZP120 (1 nmol/kg/min) in chronically catheterized, conscious rats (n = 8/group). To examine the hypothesis that ZP120 induces direct renal effects by modifying the activity of sodium transporters in the distal convoluted tubules or in the collecting ducts, ZP120-induced antinatriuresis was examined during coadministration of an inhibitor of the NaCl cotransporter, bendroflumethiazide, or a blocker of the epithelial sodium channel, amiloride, respectively. ZP120 produced a marked antinatriuresis [fractional excretion of sodium (FENa): ZP120, 0.3 ± 0.1% versus control, 0.9 ± 0.1%; p < 0.05] in sodium-replete rats. The natriuretic response to amiloride was significantly increased in ZP120-treated rats compared with controls (ΔFENa: ZP120, 1.1 ± 0.2% versus control, 0.5 ± 0.2%; p < 0.01), whereas the effect of BFTZ was equal in ZP120-treated rats and controls. These results suggest that ZP120 exerts a direct renal NOP receptor-mediated stimulatory effect on the epithelial sodium channel in the collecting ducts.

Footnotes

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.108.144774.

  • ABBREVIATIONS: NOP, nociceptin/orphanin FQ peptide receptor; ZP120, Ac-RYYRWKKKKKKK-NH2; NCC, sodium chloride cotransporter; BFTZ, bendroflumethiazide; ENaC, epithelial sodium channel; PBS, phosphate-buffered saline; TEA, tetraethylammonium bromide; GFR, glomerular filtration rate; FE, fractional excretion; DCT, distal convoluted tubules; CNT, connecting tubules; CD, collecting duct; V, urine flow; BW, body weight; MAP, mean arterial pressure; ERPF, effective renal plasma flow; UNaV, urinary sodium excretion; AQP2, aquaporin 2; amil, amiloride.

    • Received August 14, 2008.
    • Accepted November 20, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 376 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 376, Issue 3
1 Mar 2021
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Nociceptin/Orphanin FQ Peptide Receptor Agonist Ac-RYYRWKKKKKKK-NH2 (ZP120) Induces Antinatriuresis in Rats by Stimulation of Amiloride-Sensitive Sodium Reabsorption

Ulla S. K. van Deurs, Niels Hadrup, Jørgen Søberg Petersen, Sten Christensen and Thomas E. N. Jonassen
Journal of Pharmacology and Experimental Therapeutics February 1, 2009, 328 (2) 533-539; DOI: https://doi.org/10.1124/jpet.108.144774

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Nociceptin/Orphanin FQ Peptide Receptor Agonist Ac-RYYRWKKKKKKK-NH2 (ZP120) Induces Antinatriuresis in Rats by Stimulation of Amiloride-Sensitive Sodium Reabsorption

Ulla S. K. van Deurs, Niels Hadrup, Jørgen Søberg Petersen, Sten Christensen and Thomas E. N. Jonassen
Journal of Pharmacology and Experimental Therapeutics February 1, 2009, 328 (2) 533-539; DOI: https://doi.org/10.1124/jpet.108.144774
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