Nociceptin/orphanin FQ peptide receptor agonist Ac-RYYRWKKKKKKK-NH2 (ZP120) induces antinatriuresis in rats by stimulation of amiloride-sensitive sodium reabsorption.
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-NH(2) (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 (FE(Na)): 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 (DeltaFE(Na): 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.
van Deurs
Ulla S K
US
Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark. uvd@sund.ku.dk
Hadrup
Niels
N
Petersen
Jørgen Søberg
JS
Christensen
Sten
S
Jonassen
Thomas E N
TE
D000042:Absorption / Q000187:drug effects* / Q000502:physiology; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D007150:Immunohistochemistry; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists*; D012964:Sodium / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000584:Amiloride; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D012964:Sodium; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C473470:ZP120; C000722285:Oprl1 protein, rat